WO2022061978A1 - Compound composition with anti-oxidation and anti-aging effects, preparation method therefor and application thereof - Google Patents

Compound composition with anti-oxidation and anti-aging effects, preparation method therefor and application thereof Download PDF

Info

Publication number
WO2022061978A1
WO2022061978A1 PCT/CN2020/120583 CN2020120583W WO2022061978A1 WO 2022061978 A1 WO2022061978 A1 WO 2022061978A1 CN 2020120583 W CN2020120583 W CN 2020120583W WO 2022061978 A1 WO2022061978 A1 WO 2022061978A1
Authority
WO
WIPO (PCT)
Prior art keywords
compound composition
aging
oxidation
aging effects
extract
Prior art date
Application number
PCT/CN2020/120583
Other languages
French (fr)
Chinese (zh)
Inventor
邹圣灿
张曾亮
王敏
卢赛
刘竹青
宗建成
王尚龙
Original Assignee
琛蓝(美国)营养制品股份有限公司
青岛琛蓝医药科技发展有限公司
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Application filed by 琛蓝(美国)营养制品股份有限公司, 青岛琛蓝医药科技发展有限公司 filed Critical 琛蓝(美国)营养制品股份有限公司
Priority to US17/207,740 priority Critical patent/US20220087926A1/en
Publication of WO2022061978A1 publication Critical patent/WO2022061978A1/en

Links

Images

Classifications

    • A—HUMAN NECESSITIES
    • A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
    • A23L—FOODS, FOODSTUFFS, OR NON-ALCOHOLIC BEVERAGES, NOT COVERED BY SUBCLASSES A21D OR A23B-A23J; THEIR PREPARATION OR TREATMENT, e.g. COOKING, MODIFICATION OF NUTRITIVE QUALITIES, PHYSICAL TREATMENT; PRESERVATION OF FOODS OR FOODSTUFFS, IN GENERAL
    • A23L33/00—Modifying nutritive qualities of foods; Dietetic products; Preparation or treatment thereof
    • A—HUMAN NECESSITIES
    • A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
    • A23L—FOODS, FOODSTUFFS, OR NON-ALCOHOLIC BEVERAGES, NOT COVERED BY SUBCLASSES A21D OR A23B-A23J; THEIR PREPARATION OR TREATMENT, e.g. COOKING, MODIFICATION OF NUTRITIVE QUALITIES, PHYSICAL TREATMENT; PRESERVATION OF FOODS OR FOODSTUFFS, IN GENERAL
    • A23L33/00—Modifying nutritive qualities of foods; Dietetic products; Preparation or treatment thereof
    • A23L33/10—Modifying nutritive qualities of foods; Dietetic products; Preparation or treatment thereof using additives
    • A23L33/105—Plant extracts, their artificial duplicates or their derivatives
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K35/00—Medicinal preparations containing materials or reaction products thereof with undetermined constitution
    • A61K35/56—Materials from animals other than mammals
    • A61K35/63—Arthropods
    • A61K35/64—Insects, e.g. bees, wasps or fleas
    • A61K35/644—Beeswax; Propolis; Royal jelly; Honey
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K36/00—Medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicines
    • A61K36/06—Fungi, e.g. yeasts
    • A61K36/07—Basidiomycota, e.g. Cryptococcus
    • A61K36/076—Poria
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K36/00—Medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicines
    • A61K36/18—Magnoliophyta (angiosperms)
    • A61K36/185—Magnoliopsida (dicotyledons)
    • A61K36/25—Araliaceae (Ginseng family), e.g. ivy, aralia, schefflera or tetrapanax
    • A61K36/258—Panax (ginseng)
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K36/00—Medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicines
    • A61K36/18—Magnoliophyta (angiosperms)
    • A61K36/185—Magnoliopsida (dicotyledons)
    • A61K36/34—Campanulaceae (Bellflower family)
    • A61K36/344—Codonopsis
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K36/00—Medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicines
    • A61K36/18—Magnoliophyta (angiosperms)
    • A61K36/185—Magnoliopsida (dicotyledons)
    • A61K36/53—Lamiaceae or Labiatae (Mint family), e.g. thyme, rosemary or lavender
    • A61K36/537—Salvia (sage)
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K36/00—Medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicines
    • A61K36/18—Magnoliophyta (angiosperms)
    • A61K36/185—Magnoliopsida (dicotyledons)
    • A61K36/64—Orobanchaceae (Broom-rape family)
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K36/00—Medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicines
    • A61K36/18—Magnoliophyta (angiosperms)
    • A61K36/185—Magnoliopsida (dicotyledons)
    • A61K36/73—Rosaceae (Rose family), e.g. strawberry, chokeberry, blackberry, pear or firethorn
    • A61K36/736—Prunus, e.g. plum, cherry, peach, apricot or almond
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K36/00—Medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicines
    • A61K36/18—Magnoliophyta (angiosperms)
    • A61K36/185—Magnoliopsida (dicotyledons)
    • A61K36/80—Scrophulariaceae (Figwort family)
    • A61K36/804—Rehmannia
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K36/00—Medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicines
    • A61K36/18—Magnoliophyta (angiosperms)
    • A61K36/88—Liliopsida (monocotyledons)
    • A61K36/896—Liliaceae (Lily family), e.g. daylily, plantain lily, Hyacinth or narcissus
    • A61K36/8968—Ophiopogon (Lilyturf)
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P39/00—General protective or antinoxious agents
    • A61P39/06—Free radical scavengers or antioxidants
    • A—HUMAN NECESSITIES
    • A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
    • A23V—INDEXING SCHEME RELATING TO FOODS, FOODSTUFFS OR NON-ALCOHOLIC BEVERAGES AND LACTIC OR PROPIONIC ACID BACTERIA USED IN FOODSTUFFS OR FOOD PREPARATION
    • A23V2002/00—Food compositions, function of food ingredients or processes for food or foodstuffs
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K2236/00—Isolation or extraction methods of medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicine
    • A61K2236/30—Extraction of the material
    • A61K2236/33—Extraction of the material involving extraction with hydrophilic solvents, e.g. lower alcohols, esters or ketones
    • A61K2236/333—Extraction of the material involving extraction with hydrophilic solvents, e.g. lower alcohols, esters or ketones using mixed solvents, e.g. 70% EtOH
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K2236/00—Isolation or extraction methods of medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicine
    • A61K2236/30—Extraction of the material
    • A61K2236/39—Complex extraction schemes, e.g. fractionation or repeated extraction steps
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K2236/00—Isolation or extraction methods of medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicine
    • A61K2236/50—Methods involving additional extraction steps
    • A61K2236/51—Concentration or drying of the extract, e.g. Lyophilisation, freeze-drying or spray-drying

Definitions

  • the invention belongs to the technical field of natural medicines, in particular to a compound composition, a preparation method and application thereof, and in particular to a compound composition with antioxidative and anti-aging effects, and a preparation method and application thereof.
  • Kidney deficiency and spleen deficiency can lead to aging, blood stasis and phlegm can also lead to aging; and the methods of invigorating the kidney, strengthening the spleen and nourishing qi, promoting blood circulation and removing blood stasis, and removing phlegm can all cause aging. anti aging.
  • tonifying the kidney, strengthening the spleen and nourishing qi is the basic way to delay aging, and promoting blood circulation and resolving phlegm is an important method to delay aging. It is concentrated in the two categories of phlegm and blood stasis.
  • telomeres serve as the substrate of telomerase to ensure the integrity of chromosome replication and determine the lifespan of cells; and telomere length is related to the number of cell divisions and lifespan limit, scientists expressed telomerase in senescent cells , not only reversed cell senescence, but also began to use glucose to synthesize nucleotides.
  • the regulation of senescence depends on the regulation of telomeres by telomerase and the combined work of telomeres and telomerase.
  • the existing anti-aging products on the market mostly start with scavenging free radicals, and the existing free radical scavengers are mainly some single extracts or vitamin products, such as Grape seed extract, resveratrol, astaxanthin, vitamin E, etc., have very limited ability to scavenge free radicals, and the range of free radicals that can be scavenged is narrow, which cannot effectively scavenge all free radicals, so it is difficult to really make up for it. Due to the decline in the ability to scavenge free radicals caused by aging, the specific aging characteristics, the content of aging-related enzymes in the human body, and the changes of regulatory factors have not been studied in depth.
  • the purpose of the present invention is to address the problems existing in the prior art, and provide a compound composition with anti-oxidation and anti-aging effects, which has no toxic side effects, is easy to absorb, and can be used as a dietary supplement or Health food raw materials, used to delay aging, repair DNA damage, resist oxidative damage, and reduce the risk of geriatric diseases.
  • the present invention effectively delays aging from two aspects of traditional Chinese medicine and modern science through the organic combination of traditional Chinese medicine compound Qiongyu paste flavoring and marine modern component chitosan oligosaccharide.
  • Qiongyu ointment has the effects of nourishing yin and moistening the lungs, invigorating the spleen and strengthening the lungs, and the added Cistanche and Salvia can delay aging from many aspects; and the present invention is Qiongyu
  • the application of ointment has developed a new way.
  • a compound composition with anti-oxidation and anti-aging effects is prepared by mixing Chinese medicinal extracts and chitosan oligosaccharides in a mass ratio of (3-8):1;
  • the traditional Chinese medicine extract is obtained by mixing the following Chinese medicinal materials after separate extraction, in terms of mass percentage:
  • Codonopsis 0 to 10%
  • Ophiopogon japonicus 0 to 10%.
  • the traditional Chinese medicine extract is obtained by mixing the following Chinese medicinal materials after separate extraction, in terms of mass percentage:
  • the Chinese herbal medicine extract is obtained by mixing the following Chinese herbal medicines after separate extraction, in terms of mass percentage:
  • the daily dosage of the compound composition extracted and prepared by the process disclosed in the present invention is 1.8-3.6 g, and the effective dosage of the compound composition is obtained by screening according to the later animal efficacy test. .
  • the traditional Chinese medicinal materials used in the traditional Chinese medicine extract disclosed by the present invention are based on the scientific basis, and the traditional Chinese medicinal extract and index components to be added are determined according to the traditional Chinese medicine formula, network pharmacology, and Chinese Pharmacopoeia, specifically:
  • the added Chinese medicinal materials are 4-5 kinds of ginseng, Poria, Rehmannia glutinosa, Cistanche, Salvia, Codonopsis, peach kernel and Ophiopogon japonicus.
  • Ginseng is sweet, slightly bitter, slightly warm, and returns to the heart, lung, and spleen meridians. Greatly invigorating vitality, invigorating the spleen and benefiting the lungs, promoting body fluid and quenching thirst, soothing the mind and improving wisdom. Ginseng is listed as a top-grade drug in the "Shen Nong's Materia Medica", which has the effect of "doing it for a long time will not hurt the body, lighten the body and benefit the qi without aging".
  • Clinical uses 1 For the critical condition of qi deficiency and weak pulse; 2 For the symptoms of shortness of breath, shortness of breath, sluggish speech, and spontaneous perspiration due to deficiency of lung qi; 3 For fatigue and fatigue due to insufficient spleen , Eating less and loose stools and other symptoms; 4 It is used for fever, thirst and thirst caused by two injuries of Qi and Jin;
  • Poria sweet, mild, neutral in nature, and returns to the heart, lung, spleen, and kidney meridians. Invigorating the spleen and calming the heart.
  • “Compendium of Materia Medica” records "Poria's smell is light and infiltrating, its nature is upward, it produces body fluid, opens the stomach, nourishes the water source and descends, and facilitates urination. Therefore, Zhang Jiegu said that it belongs to the yang, floats and rises, and speaks of its nature; Yuan calls it the yin within the yang, descending and descending, and it is said that its merit is also called.”
  • Rehmannia glutinosa sweet, cold. Return to the heart, liver and kidney meridians. Nourishes yin and kidney, nourishes blood, and cools blood. It is quite beneficial for people with yin deficiency, blood deficiency and kidney deficiency to eat it.
  • the "Outline” contains "filling bone marrow, growing muscles, producing sperm and blood, nourishing five internal organs, insufficiency of internal injuries, clearing blood vessels, sharpening ears and eyes, black beard and hair, men's five labors and seven injuries, women's injury, leakage of cells, irregular menstruation, fetal birth All diseases".
  • Cistanche deserticola sweet; salty; warm in nature, belonging to the kidney and large intestine meridians. Invigorating kidney yang, nourishing essence and blood, moistening intestines. It has the functions of anti-aging, adjusting endocrine, promoting metabolism and strengthening, improving immunity, promoting the synthesis of deoxyribonucleic acid, and reducing blood pressure.
  • "Shen Nong's Materia Medica” records that "maintains five labors and seven injuries, replenishes the middle, removes cold and heat pain in the stem, nourishes the five internal organs, strengthens the yin, replenishes the essence and qi, and women's symptoms.”
  • Salvia bitter in taste, slightly cold.
  • Heart liver meridian. Promotes blood circulation and removes blood stasis, clears the heart and relieves pain, cools blood and eliminates carbuncle. It is used for chest pain and heartache, abdominal and flank pain, accumulation of symptoms, heat pain, restlessness, insomnia, irregular menstruation, dysmenorrhea, amenorrhea, sore swelling and pain.
  • “Compendium of Materia Medica” records "promoting blood circulation, Tongxin envelope, treatment of colic.”
  • Bie Lu contains "nourishing blood, eliminating chronic diseases of confidants and qi, lumbar spine and foot paralysis, eliminating wind and pathogens and retaining heat. Long service is beneficial to people”.
  • Codonopsis Gan, Ping. Buzhong Yiqi, and stomach Shengjin, expectorant cough.
  • Peach kernel bitter, sweet, flat. Return to the heart, liver and large intestine meridians. Promote blood circulation and remove blood stasis, moisten the intestines and relieve constipation, relieve cough and relieve asthma.
  • Ophiopogon japonicus Sweet, slightly bitter, slightly cold in nature, it returns to the stomach, lung, and heart meridians, and has the effects of nourishing yin and moistening the lungs, benefiting the stomach and producing fluid, clearing the heart and eliminating vexation.
  • "Shen Nong's Materia Medica” lists Ophiopogon japonicus as the top grade for nourishing yin and moistening the lungs, saying that it "takes a long time to lighten the body, and it is not old and not hungry".
  • Qiongyu paste is composed of ginseng, rehmannia glutinosa, white Poria, and honey. It is from Song “Hong's Collection of Prescriptions”. Yuan Wang Haogu's “Yi Lei Yuanrong” called this paste: “filling the essence and replenishing the marrow, it turns white and black. , rejuvenate the youth, walk like a flying feather.” Ming Li Shizhen's “Compendium of Materia Medica”, “Continuous clothing is happy and intellectual, white and black, teeth fall and regenerate, fasting and longevity".
  • the present invention is based on Jiawei Qiongyu paste, strictly follows the principle of compatibility between the monarch, ministers, ministers and envoys. , Rehmannia glutinosa nourishes kidney yin, the two are minister medicines, yin and yang are supplemented, and help the monarch's medicine to consolidate the root and revitalize the yuan; use Poria to strengthen the spleen and dampness, to prevent tiredness and internal dampness; Eliminate vexation to help qi and blood run, so that the supplement is not stagnant; use Codonopsis pilosula to invigorate the middle and invigorate qi, harmonize the stomach and produce body fluid; use peach kernel to activate blood and remove blood stasis; use Ophiopogon japonicus to nourish yin and moisten the lungs, clear the heart and eliminate vexation; all of the above flavors are used as adjuvant.
  • Combination of various medicines can supplement qi, blood, yin and yang, and viscera, and perform the functions of invigorating qi and producing body fluid, invigorating kidney and essence, nourishing blood and activating blood, soothing the nerves and improving wisdom.
  • chitosan oligosaccharide has the advantages of diverse functions, wide sources, strong specificity, and low toxicity and side effects. It has gradually become a research hotspot in the 21st century and is widely used in food, cosmetics, biomedicine and other fields. . It is the only positively charged and alkaline oligosaccharide in nature. It not only has strong adsorption capacity for all kinds of negatively charged toxic substances in the body, but also has reducibility, and its alkalinity can neutralize acidic substances. , Improve physical fitness, can be specifically combined with cells, improve immunity.
  • synergy is a common reaction between active substances. As early as the 1980s, it was discovered that there was synergy between different substances, especially traditional Chinese medicine complexes, as a complex system with diverse components. , There may be a certain synergistic effect between different ingredients, if the addition ratio is appropriate, the efficacy of the whole food can be improved. Therefore, the present invention utilizes the synergistic effect of the traditional Chinese medicine extract polysaccharides, saponins, flavonoids, etc. and the marine oligosaccharide chitosan oligosaccharide to achieve the technical effect of delaying aging on the basis of modern medicine.
  • the prescription is an organic whole after the combination of multiple herbs for the disease, and its medicinal effect is not equal to the amount of each flavor based on the commonly used amount.
  • Simple superposition according to the commonly used amount of each traditional Chinese medicine, it is usually not possible to determine the amount of the drug in the prescription.
  • the proportion of medicinal materials is determined by various considerations such as the characteristics of the medicinal materials, the compatibility of the monarch, ministers, assistants and envoys. It is not a simple method of comparison and orthogonality. Such experimental means can be optimally obtained.
  • Another object of the present invention is to provide a preparation method of a compound composition with anti-oxidative and anti-aging effects, comprising: extracting, purifying, and After concentrating and spray-drying to obtain the traditional Chinese medicine extract, it is evenly mixed with chitosan oligosaccharide to obtain; the specific steps are as follows:
  • step (1) spray-drying or vacuum-drying after purifying and concentrating the described extract that step (1) is merged, obtain Chinese medicine extract by sieving;
  • step (3) Mixing the traditional Chinese medicine extract in step (2) with the chitosan oligosaccharide according to the mass ratio disclosed above to obtain a compound composition with anti-oxidation and anti-aging effects.
  • the number of Chinese medicinal materials crushed and sieved is 20-80 meshes
  • the volume ratio of the added Chinese medicinal materials to the ethanol solution is 1:(5-20)
  • the number of times of heating and refluxing extraction of the traditional Chinese medicinal materials is 1 to 3 times
  • the extraction time is 1 to 3 hours
  • the extraction temperature is 80°C to 100°C.
  • the spray drying temperature is set to be 180°C to 200°C
  • the vacuum drying temperature is 50°C to 100°C
  • the sieving mesh number is 60 to 80 meshes.
  • the step (2) further includes the step of adding ⁇ -cyclodextrin to the concentrated extract before spray drying or vacuum drying to mix evenly; wherein the amount of ⁇ -cyclodextrin added is the Chinese medicinal material. 1 to 20% of the mass.
  • Another object of the present invention is to provide the application of the above disclosed compound composition with anti-oxidative and anti-aging effects in the preparation of health care products.
  • the compound composition can be used as a raw material for dietary supplements or health food to increase the content of telomerase and delay aging, and the dosage form of the compound composition is capsules, granules or tablets.
  • the present invention provides a compound composition with anti-oxidation and anti-aging effects and a preparation method and application thereof, which have the following excellent effects:
  • the present invention adopts the preparation process of separate extraction of medicinal materials, which is more stable in extraction quality and higher in controllability than traditional Chinese medicine extraction methods.
  • the compound composition disclosed and protected by the present invention has good anti-oxidation, anti-aging and increasing telomerase content through pharmacodynamic experiments.
  • the compound composition disclosed and protected in the present invention has no toxic side effects and is easy to absorb, and can be used for delaying aging, repairing DNA damage, resisting oxidative damage, and reducing the risk of geriatric diseases, and the compound composition disclosed in the present invention can be used as a meal Supplements or health food raw materials to increase telomerase content and delay aging, it can be seen that the compound composition disclosed in the present invention is suitable for promotion and application.
  • the invention discloses the adoption of various granulation and preparation processes, which can not only effectively improve the hygroscopicity of the preparation, ensure the stability of the finished product, but also increase the efficacy of the drug, so as to finally improve the effect of the finished compound composition.
  • Fig. 1 is a graph showing the scavenging ability of the compound composition of the present invention to DPPH free radicals.
  • Figure 2 is a graph showing the scavenging ability of the compound composition of the present invention to hydroxyl radicals.
  • the embodiment of the present invention discloses a compound composition with no toxic side effects and easy absorption.
  • the compound composition can be used as a dietary supplement or a health food raw material for anti-oxidation and anti-aging, and the compound composition can also improve telomeres. Enzyme content, repair DNA damage, anti-oxidative damage, reduce the risk of geriatric disease, suitable for market promotion.
  • Chitooligosaccharide 50g, ginseng: 100g, Poria: 200g, Rehmannia glutinosa: 166g, Cistanche: 168g, Salvia miltiorrhiza: 100g, Magnesium stearate: 5g.
  • ginseng medicinal materials were crushed into coarse particles (passed through a 20-mesh sieve), added with 8 times the amount of 70% ethanol, extracted twice by heating under reflux for 3 hours each time, combined with the extracts, purified, concentrated, and added with 10% ⁇ -cyclodextrin , spray-dried at 200°C, and passed through an 80-mesh sieve to obtain ginseng extract;
  • Poria cocos extract (2) The medicinal materials of Poria are pulverized (passed through an 80-mesh sieve), and 10 times the amount of water was added, and heated and refluxed for extraction once. The extraction time was 100 min. Filter, add 10% ⁇ -cyclodextrin, spray dry at 200°C, and pass through an 80-mesh sieve to obtain Poria cocos extract;
  • Cistanche Cistanche extract Pulverize the medicinal materials of Cistanche deserticola (pass through a 20-mesh sieve), add 8 times the amount of 75% ethanol, extract under reflux for 2 times, 1 hour each time, combine the extracts, purify, concentrate, add 10% ⁇ -cyclodextrin, 200 °C Spray dry, pass through an 80-mesh sieve to obtain Cistanche Cistanche extract;
  • Chitooligosaccharide 40g, ginseng: 72g, Poria: 144g, Rehmannia glutinosa: 120g, Cistanche: 180g, Salvia: 72g, Magnesium stearate: 5g.
  • Ginseng medicinal materials were crushed into coarse particles (passed through a 20-mesh sieve), added with 6 times the amount of 75% ethanol, extracted twice by heating under reflux for 3 hours each time, combined with the extracts, purified, concentrated, and added with 10% ⁇ -cyclodextrin , spray-dried at 200°C, and passed through an 80-mesh sieve to obtain ginseng extract;
  • Poria cocos extract (2) The medicinal materials of Poria are pulverized (passed through an 80-mesh sieve), added with 8 times the amount of water, heated and refluxed for extraction once, and the extraction time was 120 min. Filter, add 10% ⁇ -cyclodextrin, spray dry at 200°C, and pass through an 80-mesh sieve to obtain Poria cocos extract;
  • Cistanche Cistanche extract Pulverize the medicinal materials of Cistanche deserticola (pass through a 20-mesh sieve), add 6 times the amount of 80% ethanol, extract under reflux for 2 times, 1 hour each time, combine the extracts, purify, concentrate, add 10% ⁇ -cyclodextrin, 200 °C Spray dry, pass through an 80-mesh sieve to obtain Cistanche Cistanche extract;
  • Chitosan oligosaccharide 30g, Ginseng: 63g, Poria: 105g, Rehmannia glutinosa: 84g, Cistanche: 157g, Salvia: 63g, Codonopsis: 52.5g, Peach kernel: 52.5g, Magnesium stearate: 5g.
  • Ginseng medicinal materials were crushed into coarse particles (passed through a 20-mesh sieve), added with 4 times the amount of 80% ethanol, extracted twice by heating under reflux for 3 hours each time, combined with the extracts, purified, concentrated, and added with 10% ⁇ -cyclodextrin , spray-dried at 200°C, and passed through an 80-mesh sieve to obtain ginseng extract;
  • Cistanche Cistanche extract Pulverize the medicinal materials of Cistanche deserticola (pass through a 20-mesh sieve), add 6 times the amount of 80% ethanol, extract under reflux for 2 times, 1 hour each time, combine the extracts, purify, concentrate, add 10% ⁇ -cyclodextrin, 200 °C Spray dry, pass through an 80-mesh sieve to obtain Cistanche Cistanche extract;
  • Codonopsis pilosula The medicinal materials of Codonopsis pilosula were crushed (passed through a 20-mesh sieve), added with 8 times the amount of 60% ethanol, extracted once under reflux for 40 minutes, purified, concentrated, added with 10% ⁇ -cyclodextrin, spray-dried at 200°C, and passed through 80 mesh sieve to get Codonopsis extract
  • Example 1 Using the compound preparation prepared in Example 1 and other pharmaceutical formulations, the in vitro antioxidant effect of the compound of the present invention was tested.
  • Test substance A 50g of chitosan oligosaccharide, 100g of ginseng, 200g of Poria, 166g of Rehmannia glutinosa, 168g of Cistanche, 100g of Salvia miltiorrhiza, 5g of magnesium stearate, prepared according to the method of Example 1 to 100 times the daily prescription dose;
  • Test substance B 50 g of chitosan oligosaccharide, 100 g of ginseng, 200 g of Poria, 166 g of Rehmannia glutinosa, 168 g of Cistanche, 33.3 g of ⁇ -cyclodextrin, 5 g of magnesium stearate, prepared according to the method of Example 1 to 100 double the daily prescribed dose;
  • Test substance C 50g of chitosan oligosaccharide, 100g of ginseng, 200g of Poria, 166g of Rehmannia, Codonopsis: 168g, peach kernel: 60g, magnesium stearate: 5g, prepared according to the method of Example 1 to 100 times the daily prescription dose ;
  • Test substance D 50 g of chitosan oligosaccharide, 100 g of ginseng, 200 g of Poria, 166 g of Rehmannia glutinosa, 100 g of Salvia miltiorrhiza, 168 g of Codonopsis, and 5 g of magnesium stearate, prepared according to the method of Example 1 to prepare a 100 times daily prescription dose.
  • Test substance E 50g of chitosan oligosaccharide, 100g of ginseng, 200g of Poria, 166g of Rehmannia, 89.3g of ⁇ -cyclodextrin, 5g of magnesium stearate, prepared according to the method of Example 1 to 100 times the daily prescription dose .
  • test samples Dilute the above test substances A-E with distilled water to 4 steps of mass concentration of 10, 30, 50 and 100 mg/mL.
  • a 1 is the absorbance value of the sample without DPPH solution
  • a 2 is the absorbance value of the DPPH solution and the sample.
  • a 1 is the absorbance value of distilled water instead of H 2 O 2 ;
  • a 2 is the absorbance value of the hydroxyl radical system and the sample.
  • DPPH is a stable nitrogen-centered free radical with a strong absorption peak at 517nm.
  • the electrons or hydrogen atoms provided by antioxidants react with DPPH ⁇ , resulting in a smaller absorbance value at 517nm. According to the absorbance value The changes reflect the antioxidant capacity of antioxidants.
  • test substance A has the best antioxidant effect.
  • Hydroxyl radicals are the most reactive chemical species in the reactive oxygen species system, which can easily cross cell membranes, readily react with biomolecules such as carbohydrates, proteins, lipids, nucleic acids, and almost any biological component in cells and induce tissue damage or cause cell death.
  • the present invention has a significant antioxidant effect.
  • the indexes of the test substance group A were obviously better than those of the other groups, that is, the antioxidant effect of the compound composition composed of chitosan oligosaccharide, ginseng, Poria, Rehmannia glutinosa, Cistanche deserticola, and Salvia miltiorrhiza was obviously better than that of chitosan oligosaccharide.
  • Inclusion criteria 50-75 years old, persons with frailty, physical strength and energy due to normal aging or disease;
  • Exclusion criteria Persons with the following diseases; chronic allergic enteritis or functional diarrhea; autoimmune disease or immunodeficiency; diagnosed HIV, hepatitis B or C positive; diagnosed with a history of severe heart, lung, kidney and liver dysfunction; Major cardiovascular disease within a month; medically diagnosed neuropsychological disease or cognitive impairment; alcoholism, high alcohol intake.
  • Dosage and method 2 times a day, 3 capsules each time, the dosage is 3.6g/day, for 90 consecutive days
  • 1Blood routine red blood cell count, mean red blood cell volume, red blood cell distribution width, mean hemoglobin content, mean red blood cell hemoglobin concentration, white blood cell count, monocyte count, monocyte ratio, neutrophil count, lymphocyte ratio, mean platelet volume , platelet count;
  • liver function test total bilirubin, total protein, albumin, globulin, albumin/globulin ratio, aspartate aminotransferase, alanine aminotransferase, etc.;
  • nitric oxide NO
  • VEGF vascular endothelial growth factor
  • SOD Serum superoxide dismutase
  • TE telomerase
  • Aging symptoms There are 4 symptoms of poor energy and physical strength (fatigue after walking or activities, poor energy and physical strength in daily life, dizziness, poor sleep), which are divided into grades I-IV according to the severity, and the integral value is calculated.
  • Grade I (0 points): maintain a certain amount of exercise, and be energetic; daily energy; rarely dizziness, which occurs only after overwork; fall asleep within 30 minutes, sleep for more than 5 hours, not easy to wake up, and not sleepy during the day.
  • Grade II Slight feeling of fatigue after more walking activities (such as walking 2km); slight feeling of fatigue, daily activities are not affected; dizziness occurs only once or twice a month, and life is basically not affected; Fall asleep within 30 minutes, sleep less than 5 hours, and not feel sleepy during the day.
  • Grade III (2 points): feeling between II and IV; easily fatigued, and daily activities are affected to a certain extent; dizziness occurs once or twice a week, aggravated after exertion, affecting daily life; falling asleep more than 30 minutes, less sleep time In 5 hours, it is easy to be awakened and sleepy at a fixed time during the day.
  • Grade IV (3 points): weak back, dizziness, weakness of limbs; severe fatigue, severe limitation of daily activities; dizziness every day, aggravated after a little activity, seriously affecting daily life; more than 30 minutes Fall asleep, sleep time is less than 5 hours, often wake up in the middle of the night for no reason, and often feel sleepy during the day.
  • Grade II (1 point): low desire to eat, but can eat normally; mild chills; mild anemia, which does not affect life after nutritional supplementation; mild pain; mental restlessness/palpitations only once or twice a month, capable of normal daily life During physical activity, palpitations are aggravated; occasionally catch a cold, and it is easy to get sick only after changing seasons or exertion.
  • Grade III Difficulty eating, at risk of malnutrition; severe chills, significantly different from normal people; moderate anemia; severe pain in specific parts; mental restlessness/palpitations, activity once or twice a week Slightly larger (walking 2km), severe palpitations, accompanied by mental restlessness; the frequency of colds is between II and IV.
  • Grade IV No appetite at all, severe malnutrition; extreme chills, seriously affecting life; severe anemia, requiring drugs to maintain normal life; body pain, seriously affecting the quality of life; daily heart palpitations, mental stress, mild activity Feeling palpitations; frequent colds, frequent illnesses, and poor immunity.
  • the compound composition has an improving effect on the symptoms of aging, senile diseases and sub-health symptoms, and along with the prolongation of the taking time, its effective rate is also gradually increased; after taking the compound composition for 60 days, The total effective rate for improving aging symptoms can reach 100%, indicating that the compound composition of the present invention has a very significant improving effect on aging.
  • the above-mentioned table 7 detects the skin condition of the subject and finds that the compound composition has a certain improvement effect on the skin elasticity, collagen and melanin abnormal conditions of the elderly, and the improvement effective rate increases with the prolongation of taking time.
  • Table 8 The effect of compound composition on improving the content of anti-aging enzymes in the elderly
  • the above-mentioned table 8 detects the anti-aging enzyme content in the subject's body and finds that the longer the compound composition is taken, the higher the content of superoxide dismutase and telomerase in its body, indicating that the compound composition of the present invention can be effective. Increase the content of anti-aging enzymes in the elderly.
  • the effective rate of the compound composition disclosed and protected in the present invention for improving anti-aging enzymes in the elderly reached the highest on the 90th day of the test, and the effective rates of superoxide dismutase and telomerase were respectively 90.08 %, 86.07%, indicating that the compound composition of the present invention can gradually improve the effective rate of anti-aging enzymes in the elderly with the prolongation of taking time, and has a good anti-oxidation effect.
  • Table 10 The effect of compound composition on improving the content of vascular regulatory factors in the elderly
  • the compound composition disclosed and protected in the present invention has a significant anti-aging effect, can effectively improve the aging signs of the elderly, including aging, disease and sub-health symptoms, and has a very high effective rate, and the overall effective rate can reach 100%; it can effectively improve the skin condition of the elderly, and at the same time, it can enhance the content of anti-aging enzymes and vascular regulatory factors in the elderly.
  • the compound composition has no toxic and side effects, is easy to absorb, and can be used to delay aging, repair DNA damage, resist oxidative damage, and reduce senile diseases.
  • the risk of occurrence is suitable for market promotion and application.

Abstract

A compound composition with anti-oxidation and anti-aging effects, formed by mixing a traditional Chinese medicine extract and chitosan oligosaccharide in a weight ratio of (3-8):1. The traditional Chinese medicine extract is formed by individually extracting the following traditional Chinese medicinal materials and then mixing in percentage by weight: 7-15% of ginseng, 14-35% of poria cocos, 14-35% of radix rehmanniae, 14-35% of herba cistanche, 7-15% of radix salviae miltiorrhizae, 0-10% of radix codonopsis, 0-10% of peach seed, and 0-10% of radix ophiopogonis. The compound composition has no toxic and side effects, is easy to absorb, and can be used for delaying aging, repairing DNA damage and resisting oxidative damage, and can reduce risk of age-related diseases, and thus can be used as dietary supplements or health food ingredients to improve the content of telomerase and delay aging, and is suitable for promotion and application.

Description

一种具有抗氧化、延缓衰老功效的复方组合物及其制备方法与应用A compound composition with anti-oxidative and anti-aging effects and its preparation method and application 技术领域technical field
本发明属于天然药物技术领域，具体为一种复方组合物及其制备方法与应用，尤其涉及一种具有抗氧化、延缓衰老功效的复方组合物及其制备方法与应用。The invention belongs to the technical field of natural medicines, in particular to a compound composition, a preparation method and application thereof, and in particular to a compound composition with antioxidative and anti-aging effects, and a preparation method and application thereof.
背景技术Background technique
传统中医认为，衰老是由多种原因所致，肾虚、脾虚可致衰老，瘀血、痰浊亦可致衰老；而补肾法、健脾益气法、活血化瘀法、化痰法均可延缓衰老。其中，补肾健脾益气是延缓衰老的基本途径，活血化痰是延缓衰老的重要方法，但虚实夹杂多因素致衰老更多见，其中“虚”多集中于脾肾两虚，“实”则集中在痰浊与瘀血两大类。Traditional Chinese medicine believes that aging is caused by a variety of reasons. Kidney deficiency and spleen deficiency can lead to aging, blood stasis and phlegm can also lead to aging; and the methods of invigorating the kidney, strengthening the spleen and nourishing qi, promoting blood circulation and removing blood stasis, and removing phlegm can all cause aging. anti aging. Among them, tonifying the kidney, strengthening the spleen and nourishing qi is the basic way to delay aging, and promoting blood circulation and resolving phlegm is an important method to delay aging. It is concentrated in the two categories of phlegm and blood stasis.
此外关于衰老原因，现代医学研究包括：衰老的自由基学说、端粒与端粒酶理论等。然而自由基水平的增加或抗氧化剂的缺失使机体抗氧化能力下降和细胞毒性增加，最终造成生物膜、氨基酸链及DNA的分子结构的不可逆改变损伤，导致机体衰老相关退行性疾病的产生，加速衰老进程；端粒作为端粒酶的底物，保证染色体复制时的完整性，决定细胞的寿命；且端粒长度与细胞分裂次数及寿命极限有关，科学家们在衰老细胞内表达了端粒酶，不仅逆转了细胞的衰老，还开始利用葡萄糖合成核苷酸，衰老的调节有赖于端粒酶对端粒的调控及端粒和端粒酶的联合作业。In addition, regarding the causes of aging, modern medical research includes: the free radical theory of aging, the theory of telomeres and telomerase, etc. However, the increase in the level of free radicals or the lack of antioxidants reduces the antioxidant capacity of the body and increases the cytotoxicity, which eventually leads to irreversible changes in the molecular structure of biofilms, amino acid chains and DNA, resulting in the generation of aging-related degenerative diseases in the body. The aging process; telomeres serve as the substrate of telomerase to ensure the integrity of chromosome replication and determine the lifespan of cells; and telomere length is related to the number of cell divisions and lifespan limit, scientists expressed telomerase in senescent cells , not only reversed cell senescence, but also began to use glucose to synthesize nucleotides. The regulation of senescence depends on the regulation of telomeres by telomerase and the combined work of telomeres and telomerase.
目前具有抗衰老功能的保健食品或食品，大多以抗氧化、增强免疫力为切入点，主要应用葡萄籽提取物、白藜芦醇、虾青素等强抗氧化物质及西洋参、枸杞子等中药提升免疫力。同时细胞衰老、基因等深层次衰老也逐步进入大众视野。鉴于衰老机制本身的复杂性和不确定性致使衰老现象不能用单一机制进行阐释，必须进行多方面多层次的深入探究。同理，延缓衰老也需从多成分、多层次、多作用机制方面入手。At present, most of the health food or food with anti-aging function are based on anti-oxidation and immunity enhancement, mainly using strong antioxidant substances such as grape seed extract, resveratrol, astaxanthin, and traditional Chinese medicines such as American ginseng and wolfberry improve the immune system. At the same time, deep-level aging such as cellular aging and genes have gradually entered the public's field of vision. In view of the complexity and uncertainty of the aging mechanism itself, the aging phenomenon cannot be explained by a single mechanism. In the same way, anti-aging also needs to start from the aspects of multi-component, multi-level and multi-action mechanism.
基于上述衰老是由多方原因造成的，现阶段，市面上已有的延缓衰老产品多从清除自由基切入，已有的自由基清除剂也主要是一些单一的提取物或维生素类产品等，如葡萄籽提取物、白藜芦醇、虾青素、维生素E等，清除自由基能力非常有限，及能够清除的自由基范围较窄，不能对所有自由基起到有效清除作用，因而难以真正弥补由于年龄增长带来的自身清除自由基能力下降问题，同时对具体的衰老表征、人体内衰老相关酶含量、调节因子的变化等未深入研究。Based on the above-mentioned aging is caused by various reasons, at this stage, the existing anti-aging products on the market mostly start with scavenging free radicals, and the existing free radical scavengers are mainly some single extracts or vitamin products, such as Grape seed extract, resveratrol, astaxanthin, vitamin E, etc., have very limited ability to scavenge free radicals, and the range of free radicals that can be scavenged is narrow, which cannot effectively scavenge all free radicals, so it is difficult to really make up for it. Due to the decline in the ability to scavenge free radicals caused by aging, the specific aging characteristics, the content of aging-related enzymes in the human body, and the changes of regulatory factors have not been studied in depth.
因此，开发一款能够促进健康的细胞老化及抗氧化，且无毒副作用、易吸收，并具有抗氧化、延缓衰老功效的复方组合物是本领域技术人员亟需解决的问题。Therefore, it is an urgent problem for those skilled in the art to develop a compound composition that can promote healthy cell aging and anti-oxidation, has no toxic side effects, is easy to absorb, and has anti-oxidative and anti-aging effects.
发明内容SUMMARY OF THE INVENTION
有鉴于此，本发明的目的是针对现有技术中存在的问题，提供一种具有抗氧化、延缓衰老功效的复方组合物，该复方组合物无毒副作用、易吸收，能够作为膳食补充剂或者保健食品原料，用于延缓衰老，修复DNA损伤、抗氧化损伤，还能降低老年病的发生风险。In view of this, the purpose of the present invention is to address the problems existing in the prior art, and provide a compound composition with anti-oxidation and anti-aging effects, which has no toxic side effects, is easy to absorb, and can be used as a dietary supplement or Health food raw materials, used to delay aging, repair DNA damage, resist oxidative damage, and reduce the risk of geriatric diseases.
为了实现上述目的，本发明采用如下技术方案：In order to achieve the above object, the present invention adopts the following technical solutions:
本发明通过中药传统复方琼玉膏加味与海洋现代成分壳寡糖的有机结合，从中医及现代科学两方面着手有效延缓衰老。通过选用经典古方琼玉膏，而琼玉膏具有滋阴润肺，补脾健肺之效，以及添加的肉苁蓉和丹参都可从多个方面起到延缓衰老的作用；且本发明为琼玉膏的应用开发出新途径。The present invention effectively delays aging from two aspects of traditional Chinese medicine and modern science through the organic combination of traditional Chinese medicine compound Qiongyu paste flavoring and marine modern component chitosan oligosaccharide. By selecting the classic ancient prescription Qiongyu ointment, Qiongyu ointment has the effects of nourishing yin and moistening the lungs, invigorating the spleen and strengthening the lungs, and the added Cistanche and Salvia can delay aging from many aspects; and the present invention is Qiongyu The application of ointment has developed a new way.
一种具有抗氧化、延缓衰老功效的复方组合物，所述复方组合物是由中药提取物与壳寡糖按照质量比(3～8)：1混合而成；A compound composition with anti-oxidation and anti-aging effects, the compound composition is prepared by mixing Chinese medicinal extracts and chitosan oligosaccharides in a mass ratio of (3-8):1;
其中，所述中药提取物是由以下中药材单独提取后混合而得，按照质量百分比计：Wherein, the traditional Chinese medicine extract is obtained by mixing the following Chinese medicinal materials after separate extraction, in terms of mass percentage:
人参7～15％；Ginseng 7～15%;
茯苓14～35％；Poria 14～35%;
地黄14～35％；Rehmannia 14～35%;
肉苁蓉14～35％；Cistanche 14～35%;
丹参7～15％；Salvia 7～15%;
党参0～10％；Codonopsis 0 to 10%;
桃仁0～10％；Peach kernel 0～10%;
麦冬0～10％。Ophiopogon japonicus 0 to 10%.
优选的，所述中药提取物是由以下中药材单独提取后混合而得，按照质量百分比计：Preferably, the traditional Chinese medicine extract is obtained by mixing the following Chinese medicinal materials after separate extraction, in terms of mass percentage:
人参12～15％；Ginseng 12～15%;
茯苓25～30％；Poria 25～30%;
地黄20～25％％； Rehmannia 20～25%%;
肉苁蓉20～25％； Cistanche 20～25%;
丹参12～15％；Salvia 12～15%;
党参2～3％；Codonopsis 2 to 3%;
桃仁1～2％；1～2% of peach kernel;
麦冬1～2％。Ophiopogon japonicus 1 to 2%.
进一步优选的，所述中药提取物是由以下中药材单独提取后混合而得，按照质量百分比计：Further preferably, the Chinese herbal medicine extract is obtained by mixing the following Chinese herbal medicines after separate extraction, in terms of mass percentage:
人参13％；Ginseng 13%;
茯苓26％；Poria 26%;
地黄22％％；Rehmannia 22%%;
肉苁蓉22％；Cistanche 22%;
丹参13％；Salvia 13%;
党参2％；Codonopsis 2%;
桃仁1％；Peach kernel 1%;
麦冬1％。Ophiopogon japonicus 1%.
值得说明的是，根据药典文献推荐的生药剂量，由本发明公开的工艺提取制备的复方组合物的日服用剂量1.8～3.6g，并根据后期动物药效试验筛选得到所述复方组合物的有效剂量。It is worth noting that, according to the crude drug dosage recommended by the pharmacopoeia literature, the daily dosage of the compound composition extracted and prepared by the process disclosed in the present invention is 1.8-3.6 g, and the effective dosage of the compound composition is obtained by screening according to the later animal efficacy test. .
此外，本发明公开的中药提取物所用中药材是通过科学的依据，根据中医经典成方、网络药理学、中国药典确定要添加的中药提取物及指标成分，具体为：In addition, the traditional Chinese medicinal materials used in the traditional Chinese medicine extract disclosed by the present invention are based on the scientific basis, and the traditional Chinese medicinal extract and index components to be added are determined according to the traditional Chinese medicine formula, network pharmacology, and Chinese Pharmacopoeia, specifically:
所添加的中药材为人参、茯苓、地黄、肉苁蓉、丹参、党参、桃仁、麦冬中的4-5种，指标成分分别为人参总皂苷或人参多糖、β-茯苓聚糖或茯苓多糖、地黄甙A、B、C、D或二氢梓醇甙或桃叶珊瑚甙、松果菊苷或肉苁蓉多糖或肉苁蓉总苷、丹参酮IIA或隐丹参酮或者丹酚酸B、党参皂苷或党参多糖、苦杏仁苷或桃仁多糖、麦冬总皂苷或高异黄酮或麦冬多糖。The added Chinese medicinal materials are 4-5 kinds of ginseng, Poria, Rehmannia glutinosa, Cistanche, Salvia, Codonopsis, peach kernel and Ophiopogon japonicus. Glycoside A, B, C, D or dihydro catalpol glycosides or aucubin, echinacoside or Cistanche polysaccharide or total glycosides of Cistanche, tanshinone IIA or cryptotanshinone or salvianolic acid B, Codonopsis saponin or Codonopsis polysaccharide, bitter Amygdalin or peach kernel polysaccharide, total saponins of Ophiopogon japonicus or high isoflavones or Ophiopogon japonicus polysaccharide.
进一步的，经中药提取物之间的有机结合，并根据中医理论配伍，而不是根据单一中药功效进行的简单叠加，具体的各种中药材的功效如下：Further, through the organic combination of Chinese herbal extracts and compatibility according to the theory of Chinese medicine, rather than the simple superposition of the effects of a single Chinese herbal medicine, the specific effects of various Chinese herbal medicines are as follows:
人参：人参甘、微苦，微温，归心、肺、脾经。大补元气，补脾益肺，生津止渴，安神益智。人参在《神农本草经》中被列为上品药物，具有“多服久服不伤身、轻身益气不老延年”的作用。Ginseng: Ginseng is sweet, slightly bitter, slightly warm, and returns to the heart, lung, and spleen meridians. Greatly invigorating vitality, invigorating the spleen and benefiting the lungs, promoting body fluid and quenching thirst, soothing the mind and improving wisdom. Ginseng is listed as a top-grade drug in the "Shen Nong's Materia Medica", which has the effect of "doing it for a long time will not hurt the body, lighten the body and benefit the qi without aging".
临床用于：①用于气虚欲脱，脉微欲绝的危重症候；②用于肺气虚弱得短气喘促，懒言声微，脉虚自汗等证；③用于脾气不足的倦怠乏力，食少便溏等证；④用于热病气津两伤之身热口渴及消渴等证；⑤用于气血亏虚的心悸，失眠，健忘等病症。Clinical uses: ① For the critical condition of qi deficiency and weak pulse; ② For the symptoms of shortness of breath, shortness of breath, sluggish speech, and spontaneous perspiration due to deficiency of lung qi; ③ For fatigue and fatigue due to insufficient spleen , Eating less and loose stools and other symptoms; ④ It is used for fever, thirst and thirst caused by two injuries of Qi and Jin;
茯苓：味甘、淡，性平，归心、肺、脾、肾经。利水渗湿，健脾，宁心。《本草纲目》记载“茯苓气味淡而渗，其性上行，生津液，开腠理，滋水源而下降，利小便，故张洁古谓其属阳，浮而升，言其性也；东垣谓其为阳中之阴，降而下，言其功也”。Poria: sweet, mild, neutral in nature, and returns to the heart, lung, spleen, and kidney meridians. Invigorating the spleen and calming the heart. "Compendium of Materia Medica" records "Poria's smell is light and infiltrating, its nature is upward, it produces body fluid, opens the stomach, nourishes the water source and descends, and facilitates urination. Therefore, Zhang Jiegu said that it belongs to the yang, floats and rises, and speaks of its nature; Yuan calls it the yin within the yang, descending and descending, and it is said that its merit is also called.”
生地黄：甘，寒。归心、肝、肾经。滋阴补肾、养血补血、凉血。凡阴虚血虚肾虚者食之，颇有益处。《纲目》有载“填骨髓，长肌肉，生精血，补五脏、内伤不足，通血脉，利耳目，黑须发，男子五劳七伤，女子伤中胞漏，经候不调，胎产百病”。Rehmannia glutinosa: sweet, cold. Return to the heart, liver and kidney meridians. Nourishes yin and kidney, nourishes blood, and cools blood. It is quite beneficial for people with yin deficiency, blood deficiency and kidney deficiency to eat it. The "Outline" contains "filling bone marrow, growing muscles, producing sperm and blood, nourishing five internal organs, insufficiency of internal injuries, clearing blood vessels, sharpening ears and eyes, black beard and hair, men's five labors and seven injuries, women's injury, leakage of cells, irregular menstruation, fetal birth All diseases".
肉苁蓉：味甘；咸；性温，归肾、大肠经。补肾阳、益精血、润肠道。具有抗衰老、调整内分泌、促进代谢及强壮、提高免疫、促进进脱氧核糖核 酸合成、降压等作用。《神农本草经》记载“主五劳七伤，补中，除茎中寒热痛，养五脏，强阴，益精气，妇人症瘕”。Cistanche deserticola: sweet; salty; warm in nature, belonging to the kidney and large intestine meridians. Invigorating kidney yang, nourishing essence and blood, moistening intestines. It has the functions of anti-aging, adjusting endocrine, promoting metabolism and strengthening, improving immunity, promoting the synthesis of deoxyribonucleic acid, and reducing blood pressure. "Shen Nong's Materia Medica" records that "maintains five labors and seven injuries, replenishes the middle, removes cold and heat pain in the stem, nourishes the five internal organs, strengthens the yin, replenishes the essence and qi, and women's symptoms."
丹参：味苦，微寒。归心、肝经。活血祛瘀，通经止痛，清心除烦，凉血消痈。用于胸痹心痛，脘腹胁痛，症瘕积聚，热痹疼痛，心烦不眠，月经不调，痛经经闭，疮疡肿痛。《本草纲目》记载“活血，通心包络，治疝痛”。《别录》有载“养血，去心腹痼疾结气，腰脊强脚痹，除风邪留热。久服利人”。Salvia: bitter in taste, slightly cold. Heart, liver meridian. Promotes blood circulation and removes blood stasis, clears the heart and relieves pain, cools blood and eliminates carbuncle. It is used for chest pain and heartache, abdominal and flank pain, accumulation of symptoms, heat pain, restlessness, insomnia, irregular menstruation, dysmenorrhea, amenorrhea, sore swelling and pain. "Compendium of Materia Medica" records "promoting blood circulation, Tongxin envelope, treatment of colic." "Bie Lu" contains "nourishing blood, eliminating chronic diseases of confidants and qi, lumbar spine and foot paralysis, eliminating wind and pathogens and retaining heat. Long service is beneficial to people".
党参：甘，平。补中益气，和胃生津，祛痰止咳。Codonopsis: Gan, Ping. Buzhong Yiqi, and stomach Shengjin, expectorant cough.
桃仁：苦、甘，平。归心、肝、大肠经。活血祛瘀，润肠通便，润肠通便，止咳平喘。Peach kernel: bitter, sweet, flat. Return to the heart, liver and large intestine meridians. Promote blood circulation and remove blood stasis, moisten the intestines and relieve constipation, relieve cough and relieve asthma.
麦冬：味甘、微苦，性微寒，归胃、肺、心经，有养阴润肺、益胃生津、清心除烦的功效。《神农本草经》将麦冬列为养阴润肺的上品，言其“久服轻身，不老不饥”。Ophiopogon japonicus: Sweet, slightly bitter, slightly cold in nature, it returns to the stomach, lung, and heart meridians, and has the effects of nourishing yin and moistening the lungs, benefiting the stomach and producing fluid, clearing the heart and eliminating vexation. "Shen Nong's Materia Medica" lists Ophiopogon japonicus as the top grade for nourishing yin and moistening the lungs, saying that it "takes a long time to lighten the body, and it is not old and not hungry".
琼玉膏由人参、生地黄、白茯苓、蜂蜜组成，出自宋·《洪氏集验方》，元·王好古《医垒元戎》中称此膏：“填精补髓，发白变黑，返老还童，行如飞羽”。明·李时珍《本草纲目》，“常服开心益智，发白返黑，齿落更生，辟谷延年”。Qiongyu paste is composed of ginseng, rehmannia glutinosa, white Poria, and honey. It is from Song "Hong's Collection of Prescriptions". Yuan Wang Haogu's "Yi Lei Yuanrong" called this paste: "filling the essence and replenishing the marrow, it turns white and black. , rejuvenate the youth, walk like a flying feather." Ming Li Shizhen's "Compendium of Materia Medica", "Continuous clothing is happy and intellectual, white and black, teeth fall and regenerate, fasting and longevity".
本发明以加味琼玉膏为基，严格遵循君臣佐使配伍原理，以人参补气生津、补脾益肺、安神益智，以大补元气，补益生津，为君；以肉苁蓉补肾阳，益精血，以生地黄滋补肾阴，二者为臣药，阴阳并补，助君药固本培元；以茯苓健脾利湿，以防滋腻、水湿内停；以丹参活血祛瘀，清心除烦以助气血运行，使补而不滞；以党参补中益气、和胃生津；以桃仁活血祛瘀；以麦冬养阴润肺、清心除烦；以上一味或几味为佐药。诸药合用，可气血阴阳、脏腑并补，行益气生津、补肾益精、养血活血、安神益智之功。The present invention is based on Jiawei Qiongyu paste, strictly follows the principle of compatibility between the monarch, ministers, ministers and envoys. , Rehmannia glutinosa nourishes kidney yin, the two are minister medicines, yin and yang are supplemented, and help the monarch's medicine to consolidate the root and revitalize the yuan; use Poria to strengthen the spleen and dampness, to prevent tiredness and internal dampness; Eliminate vexation to help qi and blood run, so that the supplement is not stagnant; use Codonopsis pilosula to invigorate the middle and invigorate qi, harmonize the stomach and produce body fluid; use peach kernel to activate blood and remove blood stasis; use Ophiopogon japonicus to nourish yin and moisten the lungs, clear the heart and eliminate vexation; all of the above flavors are used as adjuvant. Medicine. Combination of various medicines can supplement qi, blood, yin and yang, and viscera, and perform the functions of invigorating qi and producing body fluid, invigorating kidney and essence, nourishing blood and activating blood, soothing the nerves and improving wisdom.
具体地，本发明的现代医学组方原理如下所述：Specifically, the principle of modern medical prescription of the present invention is as follows:
研究表明，传统中医中含有丰富的皂苷、多糖、黄酮、多酚等功能成分，具有抗疲劳、抗肿瘤、抗氧化、免疫调节、降低血糖血脂、调节血压、抑菌及促伤口愈合等多种生理活性；例如，人参中的人参皂苷、茯苓中的茯苓多 糖、地黄甙、肉苁蓉松果菊苷、丹参酮或丹酚酸B、党参皂苷等，具有丰富的现代医学研究基础证明其具有抗氧化、支持血管健康、免疫调节等等生理功能。Studies have shown that traditional Chinese medicine is rich in saponins, polysaccharides, flavonoids, polyphenols and other functional components, with anti-fatigue, anti-tumor, anti-oxidation, immune regulation, lowering blood sugar and lipids, regulating blood pressure, inhibiting bacteria and promoting wound healing. Physiological activity; for example, ginsenosides in ginseng, tuckahoe polysaccharides in tuckahoe, rehmangoside, cistanche echinacoside, tanshinone or salvianolic acid B, codonopsis saponins, etc. Supports vascular health, immune regulation, and more.
此外，壳寡糖作为典型的海洋活性物质，具有功能多样、来源广泛、特异性强、毒副作用小等优势，已逐渐成为21世纪研究的热点，被广泛用于食品、化妆品、生物医药等领域。其是自然界中唯一带正电荷、呈碱性的低聚糖，不仅对体内呈负电的各类有毒物质有较强的吸附能力，还具有还原性，且其具有的碱性可中和酸性物质，改善体质，可与细胞特异性结合，提高免疫力。In addition, as a typical marine active substance, chitosan oligosaccharide has the advantages of diverse functions, wide sources, strong specificity, and low toxicity and side effects. It has gradually become a research hotspot in the 21st century and is widely used in food, cosmetics, biomedicine and other fields. . It is the only positively charged and alkaline oligosaccharide in nature. It not only has strong adsorption capacity for all kinds of negatively charged toxic substances in the body, but also has reducibility, and its alkalinity can neutralize acidic substances. , Improve physical fitness, can be specifically combined with cells, improve immunity.
更进一步的，协同作用是活性物质之间的一种常见反应，早在20世纪80年代，人们就发现不同物质之间存在协同作用，尤其是中药复合物，作为一种复杂的体系，成分多样，不同成分间可能存在一定协同作用，若添加比例适当，可以提升整个食品的的功效。因此，本发明利用中药提取物多糖、皂苷、黄酮等与海洋低聚糖壳寡糖的协同作用，在现代医学基础上达到延缓衰老的技术效果。Further, synergy is a common reaction between active substances. As early as the 1980s, it was discovered that there was synergy between different substances, especially traditional Chinese medicine complexes, as a complex system with diverse components. , There may be a certain synergistic effect between different ingredients, if the addition ratio is appropriate, the efficacy of the whole food can be improved. Therefore, the present invention utilizes the synergistic effect of the traditional Chinese medicine extract polysaccharides, saponins, flavonoids, etc. and the marine oligosaccharide chitosan oligosaccharide to achieve the technical effect of delaying aging on the basis of modern medicine.
另外，在现有技术中，虽然每味中药的常用量是已知的，但是方剂是针对病症对多味药配伍后的有机整体，其药效不等同于其各药味在常用量基础上的简单叠加，根据每味中药的常用量通常并不能确定其在方剂中的药量，药材用量配比由其药材特性、君臣佐使配伍等各种考虑因素决定，并非简单的通过比较法、正交法等实验手段即可优选得出。In addition, in the prior art, although the commonly used amount of each traditional Chinese medicine is known, the prescription is an organic whole after the combination of multiple herbs for the disease, and its medicinal effect is not equal to the amount of each flavor based on the commonly used amount. Simple superposition, according to the commonly used amount of each traditional Chinese medicine, it is usually not possible to determine the amount of the drug in the prescription. The proportion of medicinal materials is determined by various considerations such as the characteristics of the medicinal materials, the compatibility of the monarch, ministers, assistants and envoys. It is not a simple method of comparison and orthogonality. Such experimental means can be optimally obtained.
本发明还有一个目的，就是提供一种具有抗氧化、延缓衰老功效的复方组合物的制备方法，包括：将人参、茯苓、地黄、肉苁蓉、丹参、党参、桃仁和麦冬分别提取、纯化、浓缩及喷雾干燥制得中药提取物后与壳寡糖混合均匀制得；具体包括如下步骤：Another object of the present invention is to provide a preparation method of a compound composition with anti-oxidative and anti-aging effects, comprising: extracting, purifying, and After concentrating and spray-drying to obtain the traditional Chinese medicine extract, it is evenly mixed with chitosan oligosaccharide to obtain; the specific steps are as follows:
(1)将中药材粉碎过筛后与乙醇溶液按照配比加热回流提取、过滤，并将药渣多次提取后的提取液合并，备用；(1) After the Chinese medicinal materials are pulverized and sieved, they are heated and refluxed for extraction and filtration with ethanol solution according to the proportion, and the extracts after multiple extractions of the medicinal residues are combined for subsequent use;
(2)将步骤(1)合并的所述提取液纯化、浓缩后喷雾干燥或真空干燥，过筛得到中药提取物；(2) spray-drying or vacuum-drying after purifying and concentrating the described extract that step (1) is merged, obtain Chinese medicine extract by sieving;
(3)将步骤(2)中所述中药提取物按照上述公开的质量配比与所述壳寡糖混合均匀，得到具有抗氧化、延缓衰老功效的复方组合物。(3) Mixing the traditional Chinese medicine extract in step (2) with the chitosan oligosaccharide according to the mass ratio disclosed above to obtain a compound composition with anti-oxidation and anti-aging effects.
优选的，所述步骤(1)中，中药材粉碎过筛目数为20～80目，添加中药材与乙醇溶液的体积比为1：(5～20)，且中药材加热回流提取次数为1～3次，提取时间为1～3h，提取温度为80℃～100℃。Preferably, in the step (1), the number of Chinese medicinal materials crushed and sieved is 20-80 meshes, the volume ratio of the added Chinese medicinal materials to the ethanol solution is 1:(5-20), and the number of times of heating and refluxing extraction of the traditional Chinese medicinal materials is 1 to 3 times, the extraction time is 1 to 3 hours, and the extraction temperature is 80°C to 100°C.
优选的，所述步骤(2)中，喷雾干燥设定温度为180℃～200℃，真空干燥温度为50℃～100℃，过筛目数为60～80目。Preferably, in the step (2), the spray drying temperature is set to be 180°C to 200°C, the vacuum drying temperature is 50°C to 100°C, and the sieving mesh number is 60 to 80 meshes.
示范性的，所述步骤(2)还包括喷雾干燥或真空干燥前向浓缩后的提取液中添加β-环糊精混合均匀步骤；其中所述β-环糊精添加量为所述中药材质量的1～20％。Exemplarily, the step (2) further includes the step of adding β-cyclodextrin to the concentrated extract before spray drying or vacuum drying to mix evenly; wherein the amount of β-cyclodextrin added is the Chinese medicinal material. 1 to 20% of the mass.
此外，本发明另外一个目的是提供上述公开的一种具有抗氧化、延缓衰老功效的复方组合物在制备保健品中的应用。In addition, another object of the present invention is to provide the application of the above disclosed compound composition with anti-oxidative and anti-aging effects in the preparation of health care products.
进一步的，所述复方组合物可以作为膳食补充剂或保健食品的原料，以提高端粒酶含量、延缓衰老，且所述复方组合物的剂型为胶囊剂、颗粒剂或片剂。Further, the compound composition can be used as a raw material for dietary supplements or health food to increase the content of telomerase and delay aging, and the dosage form of the compound composition is capsules, granules or tablets.
经由上述技术方案可知，与现有技术相比，本发明提供了一种具有抗氧化、延缓衰老功效的复方组合物及其制备方法与应用，具有如下优异效果：As can be seen from the above technical solutions, compared with the prior art, the present invention provides a compound composition with anti-oxidation and anti-aging effects and a preparation method and application thereof, which have the following excellent effects:
1.本发明采用药材单独提取后复合的制备工艺，其相较传统中药提取方法提取质量更加稳定，可控性更高。1. The present invention adopts the preparation process of separate extraction of medicinal materials, which is more stable in extraction quality and higher in controllability than traditional Chinese medicine extraction methods.
2.本发明公开保护的复方组合物通过药效实验确定了其具有良好的抗氧化、延缓衰老及提高端粒酶含量的作用。2. The compound composition disclosed and protected by the present invention has good anti-oxidation, anti-aging and increasing telomerase content through pharmacodynamic experiments.
3.本发明公开保护的复方组合物无毒副作用、易吸收，用于延缓衰老，修复DNA损伤、抗氧化损伤，还能降低老年病的发生风险，并且本发明公开的复方组合物可作为膳食补充剂或保健食品原料，以提高端粒酶含量、延缓衰老，由此可见，本发明公开的复方组合物适于推广与应用。3. The compound composition disclosed and protected in the present invention has no toxic side effects and is easy to absorb, and can be used for delaying aging, repairing DNA damage, resisting oxidative damage, and reducing the risk of geriatric diseases, and the compound composition disclosed in the present invention can be used as a meal Supplements or health food raw materials to increase telomerase content and delay aging, it can be seen that the compound composition disclosed in the present invention is suitable for promotion and application.
4.本发明公开采用多种制粒及制剂工艺，不仅能有效改善制剂的吸湿性，保证成品的稳定性，还能加大药物的药效，以最终提高成品复方组合物的效果。4. The invention discloses the adoption of various granulation and preparation processes, which can not only effectively improve the hygroscopicity of the preparation, ensure the stability of the finished product, but also increase the efficacy of the drug, so as to finally improve the effect of the finished compound composition.
附图说明Description of drawings
为了更清楚地说明本发明实施例或现有技术中的技术方案，下面将对实施例或现有技术描述中所需要使用的附图作简单地介绍，显而易见地，下面描述中的附图仅仅是本发明的实施例，对于本领域普通技术人员来讲，在不付出创造性劳动的前提下，还可以根据提供的附图获得其他的附图。In order to explain the embodiments of the present invention or the technical solutions in the prior art more clearly, the following briefly introduces the accompanying drawings that need to be used in the description of the embodiments or the prior art. Obviously, the accompanying drawings in the following description are only It is an embodiment of the present invention. For those of ordinary skill in the art, other drawings can also be obtained according to the provided drawings without creative work.
图1为本发明复方组合物对DPPH自由基的清除能力图。Fig. 1 is a graph showing the scavenging ability of the compound composition of the present invention to DPPH free radicals.
图2为本发明复方组合物对羟基自由基的清除能力图。Figure 2 is a graph showing the scavenging ability of the compound composition of the present invention to hydroxyl radicals.
具体实施方式detailed description
下面将结合说明书及相应的实施例对本发明公开的技术方案进行清楚、完整地描述，显然，所描述的实施例仅是本发明一部分实施例，而不是全部的实施例。基于本发明中的实施例，本领域普通技术人员在没有做出创造性劳动前提下所获得的所有其他实施例，都属于本发明保护的范围。The technical solutions disclosed in the present invention will be clearly and completely described below with reference to the description and the corresponding embodiments. Obviously, the described embodiments are only a part of the embodiments of the present invention, rather than all the embodiments. Based on the embodiments of the present invention, all other embodiments obtained by those of ordinary skill in the art without creative efforts shall fall within the protection scope of the present invention.
本发明实施例公开了一种无毒副作用、易吸收的复方组合物，该复方组合物可作为膳食补充剂或保健食品原料用于抗氧化、延缓衰老，及该复方组合物还能提高端粒酶含量，修复DNA损伤、抗氧化损伤，降低老年病的发生风险，适于市面推广。The embodiment of the present invention discloses a compound composition with no toxic side effects and easy absorption. The compound composition can be used as a dietary supplement or a health food raw material for anti-oxidation and anti-aging, and the compound composition can also improve telomeres. Enzyme content, repair DNA damage, anti-oxidative damage, reduce the risk of geriatric disease, suitable for market promotion.
为更好地理解本发明，下面通过以下实施例对本发明作进一步具体的阐述，但不可理解为对本发明的限定，对于本领域的技术人员根据上述发明内容所作的一些非本质的改进与调整，也视为落在本发明的保护范围内。In order to better understand the present invention, the present invention will be further elaborated below through the following examples, but it should not be construed as a limitation of the present invention. For some non-essential improvements and adjustments made by those skilled in the art according to the above-mentioned content of the invention, It is also regarded as falling within the protection scope of the present invention.
下面将结合具体实施例对本发明公开的技术方案作进一步的说明。The technical solutions disclosed in the present invention will be further described below with reference to specific embodiments.
实施例1：Example 1:
一种具有抗氧化、延缓衰老功效的复方组合物组成配方如下：A compound composition with anti-oxidative and anti-aging effects is as follows:
壳寡糖：50g、人参药材：100g、茯苓药材：200g、地黄药材：166g、肉苁蓉药材：168g、丹参药材：100g、硬脂酸镁：5g。Chitooligosaccharide: 50g, ginseng: 100g, Poria: 200g, Rehmannia glutinosa: 166g, Cistanche: 168g, Salvia miltiorrhiza: 100g, Magnesium stearate: 5g.
所述复方组合物的制备方法，具体制备步骤如下：The preparation method of the compound composition, the specific preparation steps are as follows:
(1)人参药材粉碎成粗颗粒(过20目筛)加8倍量70％乙醇，加热回流提取2次，每次3小时，合并提取液，纯化、浓缩、加10％β-环糊精，200℃喷干，过80目筛，得人参提取物；(1) The ginseng medicinal materials were crushed into coarse particles (passed through a 20-mesh sieve), added with 8 times the amount of 70% ethanol, extracted twice by heating under reflux for 3 hours each time, combined with the extracts, purified, concentrated, and added with 10% β-cyclodextrin , spray-dried at 200°C, and passed through an 80-mesh sieve to obtain ginseng extract;
(2)茯苓药材粉碎(过80目筛)加10倍量的水，加热回流提取1次，提取时间为100min，提取液浓缩至原体积的1/10，采用80％浓度乙醇醇沉12h，过滤、加10％β-环糊精，200℃喷干，过80目筛，得茯苓提取物；(2) The medicinal materials of Poria are pulverized (passed through an 80-mesh sieve), and 10 times the amount of water was added, and heated and refluxed for extraction once. The extraction time was 100 min. Filter, add 10% β-cyclodextrin, spray dry at 200°C, and pass through an 80-mesh sieve to obtain Poria cocos extract;
(3)地黄药材粉碎(过20目筛)加8倍量60％乙醇，加热回流提取2次，每次1.5小时，合并提取液，纯化、浓缩、加10％β-环糊精，200℃喷干，过80目筛，得地黄提取物；(3) Pulverize the medicinal materials of Rehmannia glutinosa (pass through a 20-mesh sieve), add 8 times the amount of 60% ethanol, extract under reflux for 2 times, 1.5 hours each time, combine the extracts, purify, concentrate, add 10% β-cyclodextrin, 200 ℃ Spray dry, pass through an 80-mesh sieve to obtain Rehmannia glutinosa extract;
(4)肉苁蓉药材粉碎(过20目筛)加8倍量75％乙醇，加热回流提取2次，每次1小时，合并提取液，纯化、浓缩、加10％β-环糊精，200℃喷干，过80目筛，得肉苁蓉提取物；(4) Pulverize the medicinal materials of Cistanche deserticola (pass through a 20-mesh sieve), add 8 times the amount of 75% ethanol, extract under reflux for 2 times, 1 hour each time, combine the extracts, purify, concentrate, add 10% β-cyclodextrin, 200 ℃ Spray dry, pass through an 80-mesh sieve to obtain Cistanche Cistanche extract;
(5)丹参药材加8倍量80％乙醇，加热回流提取2次，每次1.5小时，合并提取液，纯化、浓缩、加10％β-环糊精，200℃喷干，过80目筛，得丹参提取物；(5) Add 8 times the amount of 80% ethanol to the medicinal materials of Salvia miltiorrhiza, heat and reflux for 2 times, 1.5 hours each time, combine the extracts, purify, concentrate, add 10% β-cyclodextrin, spray dry at 200°C, and pass through an 80-mesh sieve , get salvia extract;
(6)将上述的制备得到的中药提取物与壳寡糖混合均匀，制粒，填充制成复方胶囊，为100倍日处方剂量。(6) Mixing the above-prepared traditional Chinese medicine extract and chitosan oligosaccharide uniformly, granulating, filling and making compound capsules, which is 100 times the daily prescription dose.
实施例2Example 2
一种具有抗氧化、延缓衰老功效的复方组合物组成配方如下：A compound composition with anti-oxidative and anti-aging effects is as follows:
壳寡糖：40g、人参药材：72g、茯苓药材：144g、地黄药材：120g、肉苁蓉药材：180g、丹参药材：72g、硬脂酸镁：5g。Chitooligosaccharide: 40g, ginseng: 72g, Poria: 144g, Rehmannia glutinosa: 120g, Cistanche: 180g, Salvia: 72g, Magnesium stearate: 5g.
所述复方组合物的制备方法，具体制备步骤如下：The preparation method of the compound composition, the specific preparation steps are as follows:
(1)人参药材粉碎成粗颗粒(过20目筛)加6倍量75％乙醇，加热回流提取2次，每次3小时，合并提取液，纯化、浓缩、加10％β-环糊精，200℃喷干，过80目筛，得人参提取物；(1) Ginseng medicinal materials were crushed into coarse particles (passed through a 20-mesh sieve), added with 6 times the amount of 75% ethanol, extracted twice by heating under reflux for 3 hours each time, combined with the extracts, purified, concentrated, and added with 10% β-cyclodextrin , spray-dried at 200°C, and passed through an 80-mesh sieve to obtain ginseng extract;
(2)茯苓药材粉碎(过80目筛)加8倍量的水，加热回流提取1次，提取时间为120min，提取液浓缩至原体积的1/10，采用80％浓度乙醇醇沉12h，过滤、加10％β-环糊精，200℃喷干，过80目筛，得茯苓提取物；(2) The medicinal materials of Poria are pulverized (passed through an 80-mesh sieve), added with 8 times the amount of water, heated and refluxed for extraction once, and the extraction time was 120 min. Filter, add 10% β-cyclodextrin, spray dry at 200°C, and pass through an 80-mesh sieve to obtain Poria cocos extract;
(3)地黄药材粉碎(过20目筛)加10倍量70％乙醇，加热回流提取2次，每次1.5小时，合并提取液，纯化、浓缩、加10％β-环糊精，200℃喷干，过80目筛，得地黄提取物；(3) Pulverize the medicinal materials of Rehmannia glutinosa (pass through a 20-mesh sieve), add 10 times the amount of 70% ethanol, extract under reflux for 2 times, 1.5 hours each time, combine the extracts, purify, concentrate, add 10% β-cyclodextrin, 200 ℃ Spray dry, pass through an 80-mesh sieve to obtain Rehmannia glutinosa extract;
(4)肉苁蓉药材粉碎(过20目筛)加6倍量80％乙醇，加热回流提取2次，每次1小时，合并提取液，纯化、浓缩、加10％β-环糊精，200℃喷干，过80目筛，得肉苁蓉提取物；(4) Pulverize the medicinal materials of Cistanche deserticola (pass through a 20-mesh sieve), add 6 times the amount of 80% ethanol, extract under reflux for 2 times, 1 hour each time, combine the extracts, purify, concentrate, add 10% β-cyclodextrin, 200 ℃ Spray dry, pass through an 80-mesh sieve to obtain Cistanche Cistanche extract;
(5)丹参药材加8倍量80％乙醇，加热回流提取2次，每次1.5小时，合并提取液，纯化、浓缩、加10％β-环糊精，200℃喷干，过80目筛，得丹参提取物；(5) Add 8 times the amount of 80% ethanol to the medicinal materials of Salvia miltiorrhiza, heat and reflux for 2 times, 1.5 hours each time, combine the extracts, purify, concentrate, add 10% β-cyclodextrin, spray dry at 200°C, and pass through an 80-mesh sieve , get salvia extract;
(6)将上述的制备得到的提取物与壳寡糖混合均匀得中药复方组合物，混合制粒，得到中药复方组合物颗粒，为100倍日处方剂量。(6) Mixing the above-prepared extract and chitosan oligosaccharide uniformly to obtain a traditional Chinese medicine compound composition, and mixing and granulating to obtain a traditional Chinese medicine compound composition granule, which is 100 times the daily prescription dose.
实施例3Example 3
一种具有抗氧化、延缓衰老功效的复方组合物组成配方如下：A compound composition with anti-oxidative and anti-aging effects is as follows:
壳寡糖：30g、人参药材：63g、茯苓药材：105g、地黄药材：84g、肉苁蓉药材：157g、丹参药材：63g、党参：52.5g、桃仁：52.5g、硬脂酸镁：5g。Chitosan oligosaccharide: 30g, Ginseng: 63g, Poria: 105g, Rehmannia glutinosa: 84g, Cistanche: 157g, Salvia: 63g, Codonopsis: 52.5g, Peach kernel: 52.5g, Magnesium stearate: 5g.
所述复方组合物的制备方法，具体制备步骤如下：The preparation method of the compound composition, the specific preparation steps are as follows:
(1)人参药材粉碎成粗颗粒(过20目筛)加4倍量80％乙醇，加热回流提取2次，每次3小时，合并提取液，纯化、浓缩、加10％β-环糊精，200℃喷干，过80目筛，得人参提取物；(1) Ginseng medicinal materials were crushed into coarse particles (passed through a 20-mesh sieve), added with 4 times the amount of 80% ethanol, extracted twice by heating under reflux for 3 hours each time, combined with the extracts, purified, concentrated, and added with 10% β-cyclodextrin , spray-dried at 200°C, and passed through an 80-mesh sieve to obtain ginseng extract;
(2)茯苓药材粉碎(过80目筛)加6倍量的水，加热回流提取2次，每次1.5小时，提取液浓缩至原体积的1/10，采用80％浓度乙醇醇沉12h，过滤、加10％β-环糊精，200℃喷干，过80目筛，得茯苓提取物；(2) Pulverize the medicinal materials of Poria cocos (passing through an 80-mesh sieve), add 6 times the amount of water, and extract by heating and refluxing for 2 times for 1.5 hours each time. Filter, add 10% β-cyclodextrin, spray dry at 200°C, and pass through an 80-mesh sieve to obtain Poria cocos extract;
(3)地黄药材粉碎(过20目筛)加6倍量70％乙醇，加热回流提取2次，每次1.5小时，合并提取液，纯化、浓缩、加10％β-环糊精，200℃喷干，过80目筛，得地黄提取物；(3) Pulverize the medicinal materials of Rehmannia glutinosa (pass through a 20-mesh sieve), add 6 times the amount of 70% ethanol, extract under reflux for 2 times, 1.5 hours each time, combine the extracts, purify, concentrate, add 10% β-cyclodextrin, 200 ℃ Spray dry, pass through an 80-mesh sieve to obtain Rehmannia glutinosa extract;
(4)肉苁蓉药材粉碎(过20目筛)加6倍量80％乙醇，加热回流提取2次，每次1小时，合并提取液，纯化、浓缩、加10％β-环糊精，200℃喷干，过80目筛，得肉苁蓉提取物；(4) Pulverize the medicinal materials of Cistanche deserticola (pass through a 20-mesh sieve), add 6 times the amount of 80% ethanol, extract under reflux for 2 times, 1 hour each time, combine the extracts, purify, concentrate, add 10% β-cyclodextrin, 200 ℃ Spray dry, pass through an 80-mesh sieve to obtain Cistanche Cistanche extract;
(5)丹参药材加8倍量80％乙醇，加热回流提取2次，每次1.5小时，合并提取液，纯化、浓缩、加10％β-环糊精，200℃喷干，过80目筛，得丹参提取物；(5) Add 8 times the amount of 80% ethanol to the medicinal materials of Salvia miltiorrhiza, heat and reflux for 2 times, 1.5 hours each time, combine the extracts, purify, concentrate, add 10% β-cyclodextrin, spray dry at 200°C, and pass through an 80-mesh sieve , get salvia extract;
(6)党参药材粉碎(过20目筛)加8倍量60％乙醇，加热回流提取1次，时间为40分钟，纯化、浓缩、加10％β-环糊精，200℃喷干，过80目筛，得党参提取物(6) The medicinal materials of Codonopsis pilosula were crushed (passed through a 20-mesh sieve), added with 8 times the amount of 60% ethanol, extracted once under reflux for 40 minutes, purified, concentrated, added with 10% β-cyclodextrin, spray-dried at 200°C, and passed through 80 mesh sieve to get Codonopsis extract
(7)桃仁药材加10倍量的水，加热回流提取1次，时间为2小时，纯化，浓缩、加10％β-环糊精，200℃喷干，过80目筛，得桃仁提取物；(7) Add 10 times the amount of water to the medicinal materials of peach kernels, heat and reflux for extraction once for 2 hours, purify, concentrate, add 10% β-cyclodextrin, spray dry at 200°C, and pass through an 80-mesh sieve to obtain peach kernel extracts ;
(8)将上述的制备得到的提取物与壳寡糖混合均匀得中药复方组合物，干式制粒，得到中药复方组合物颗粒，为100倍日处方剂量。(8) Mixing the above-prepared extract and chitosan oligosaccharide uniformly to obtain a traditional Chinese medicine compound composition, and dry granulation to obtain a traditional Chinese medicine compound composition granule, which is 100 times the daily prescription dose.
本说明书中各个实施例采用递进的方式描述，每个实施例重点说明的都是与其他实施例的不同之处，各个实施例之间相同相似部分互相参见即可。The various embodiments in this specification are described in a progressive manner, and each embodiment focuses on the differences from other embodiments, and the same and similar parts between the various embodiments can be referred to each other.
另外，为了进一步说明本发明申请公开制备的复方组合物的药效，发明人进行如下试验用以评价：In addition, in order to further illustrate the efficacy of the compound composition disclosed in the present application, the inventors conducted the following tests to evaluate:
(一)本发明体外抗氧化作用的试验研究(1) Experimental study on the antioxidative effect in vitro of the present invention
使用实施例1中制备的复合物制剂及其他药物组方，对本发明复合物的体外抗氧化作用进行检验。Using the compound preparation prepared in Example 1 and other pharmaceutical formulations, the in vitro antioxidant effect of the compound of the present invention was tested.
1)试验样品分组：1) Test sample grouping:
供试物A：壳寡糖50g、人参药材100g、茯苓药材200g、地黄药材166g、肉苁蓉药材168g、丹参药材100g、硬脂酸镁5g，按实施例1的方法制备成100倍日处方剂量；Test substance A: 50g of chitosan oligosaccharide, 100g of ginseng, 200g of Poria, 166g of Rehmannia glutinosa, 168g of Cistanche, 100g of Salvia miltiorrhiza, 5g of magnesium stearate, prepared according to the method of Example 1 to 100 times the daily prescription dose;
供试物B：壳寡糖50g、人参药材100g、茯苓药材200g、地黄药材166g、肉苁蓉药材168g、β-环糊精33.3g、硬脂酸镁：5g，按实施例1的方法制备成100倍日处方剂量；Test substance B: 50 g of chitosan oligosaccharide, 100 g of ginseng, 200 g of Poria, 166 g of Rehmannia glutinosa, 168 g of Cistanche, 33.3 g of β-cyclodextrin, 5 g of magnesium stearate, prepared according to the method of Example 1 to 100 double the daily prescribed dose;
供试物C：壳寡糖50g、人参药材100g、茯苓药材200g、地黄药材166g、党参：168g、桃仁：60g、硬脂酸镁：5g，按实施例1的方法制备成100倍日处方剂量；Test substance C: 50g of chitosan oligosaccharide, 100g of ginseng, 200g of Poria, 166g of Rehmannia, Codonopsis: 168g, peach kernel: 60g, magnesium stearate: 5g, prepared according to the method of Example 1 to 100 times the daily prescription dose ;
供试物D：壳寡糖50g、人参药材100g、茯苓药材200g、地黄药材166g、丹参药材：100g、党参：168g、硬脂酸镁：5g，按实施例1的方法制备成100倍日处方剂量。Test substance D: 50 g of chitosan oligosaccharide, 100 g of ginseng, 200 g of Poria, 166 g of Rehmannia glutinosa, 100 g of Salvia miltiorrhiza, 168 g of Codonopsis, and 5 g of magnesium stearate, prepared according to the method of Example 1 to prepare a 100 times daily prescription dose.
供试物E：壳寡糖50g、人参药材100g、茯苓药材200g、地黄药材166g、β-环糊精89.3g、硬脂酸镁：5g，按实施例1的方法制备成100倍日处方剂量。Test substance E: 50g of chitosan oligosaccharide, 100g of ginseng, 200g of Poria, 166g of Rehmannia, 89.3g of β-cyclodextrin, 5g of magnesium stearate, prepared according to the method of Example 1 to 100 times the daily prescription dose .
试验样品配制：将上述供试物A-E用蒸馏水各自稀释成10，30，50和100mg/mL4个阶梯质量浓度。Preparation of test samples: Dilute the above test substances A-E with distilled water to 4 steps of mass concentration of 10, 30, 50 and 100 mg/mL.
2)试验方法：2) Test method:
1.DPPH自由基清除能力1. DPPH free radical scavenging ability
取1mL样品溶液与1mL DPPH-乙醇溶液(0.125mol/L)于涡旋振荡器混匀后，置于室温下避光反应30min后置于517nm下测定其吸光度值，以无水乙醇作为空白对照，记为A 0。所有样品进行3次平行测定，取平均值。DPPH自由基清除率计算公式如下： Take 1 mL of the sample solution and 1 mL of DPPH-ethanol solution (0.125mol/L) and mix it in a vortex shaker, place it at room temperature for 30 min in the dark, and then place it at 517 nm to measure its absorbance value, with absolute ethanol as a blank control , denoted as A 0 . All samples were measured three times in parallel, and the average value was taken. The formula for calculating the DPPH free radical scavenging rate is as follows:
Figure PCTCN2020120583-appb-000001
Figure PCTCN2020120583-appb-000001
其中：A 1是没有DPPH溶液的样品的吸光值；A 2是DPPH溶液与样品的吸光值。 Where: A 1 is the absorbance value of the sample without DPPH solution; A 2 is the absorbance value of the DPPH solution and the sample.
2.羟基自由基清除率的测定2. Determination of hydroxyl radical scavenging rate
取1mL样品溶液，分别加入1.0mL FeSO 4(9mmol/L)，10mL水杨酸乙醇溶液(9mmol/L)和1mL H 2O 2(9mmol/L)。在37℃避光反应1h后，测定混合物在510nm处的吸光值。无水乙醇为空白对照，记为A 0，所有样品进行3次平行测定。用公式(2)计算清除羟基自由基的能力： Take 1 mL of the sample solution and add 1.0 mL FeSO 4 (9 mmol/L), 10 mL ethanol solution of salicylic acid (9 mmol/L) and 1 mL H 2 O 2 (9 mmol/L) respectively. After reacting in the dark at 37°C for 1 h, the absorbance of the mixture at 510 nm was measured. Absolute ethanol was used as blank control, recorded as A 0 , and all samples were tested in parallel for 3 times. The ability to scavenge hydroxyl radicals is calculated using formula (2):
Figure PCTCN2020120583-appb-000002
Figure PCTCN2020120583-appb-000002
其中：A 1是蒸馏水代替H 2O 2的吸光值；A 2是羟基自由基体系与样品的吸光值。 Among them: A 1 is the absorbance value of distilled water instead of H 2 O 2 ; A 2 is the absorbance value of the hydroxyl radical system and the sample.
3)结果分析：3) Result analysis:
DPPH是一种稳定的以氮为中心的自由基，517nm处有较强的吸收峰，抗氧化剂提供的电子或氢原子与DPPH·发生反应，导致其在517nm的吸光值变小，根据吸光值的变化反映抗氧化剂的抗氧化能力。DPPH is a stable nitrogen-centered free radical with a strong absorption peak at 517nm. The electrons or hydrogen atoms provided by antioxidants react with DPPH·, resulting in a smaller absorbance value at 517nm. According to the absorbance value The changes reflect the antioxidant capacity of antioxidants.
从图1可以看出，各供试物对DPPH自由基的清除能力随着浓度的增加而增强，并且抗氧化能力：供试物A＞供试物D＞供试物C＞供试物B＞供试物E。因此可以说明供试物A的抗氧化效果最佳。It can be seen from Figure 1 that the scavenging ability of each test substance to DPPH free radicals increases with the increase of concentration, and the antioxidant capacity: test substance A > test substance D > test substance C > test substance B > Test substance E. Therefore, it can be shown that test substance A has the best antioxidant effect.
羟基自由基是活性氧系统中活性最高的化学物质，它可以很容易地穿过细胞膜，容易与生物分子如碳水化合物，蛋白质，脂质，核酸以及细胞中几乎任何生物成分发生反应并诱导组织损伤或导致细胞死亡。Hydroxyl radicals are the most reactive chemical species in the reactive oxygen species system, which can easily cross cell membranes, readily react with biomolecules such as carbohydrates, proteins, lipids, nucleic acids, and almost any biological component in cells and induce tissue damage or cause cell death.
从图2可以看出，随着供试物质量浓度的增加，各供试物对羟基自由基清除能力呈现稳定的增长，供试物A的清除能力在个质量浓度测量范围均大于其他供试物，当质量浓度为100.0mg/mL时，各供试物对羟基的清除能力达到最大。It can be seen from Figure 2 that with the increase of the mass concentration of the test substance, the scavenging ability of each test substance to hydroxyl radicals shows a steady increase, and the scavenging ability of the test substance A is greater than that of the other tests in each mass concentration measurement range. When the mass concentration was 100.0 mg/mL, the scavenging ability of each test substance to hydroxyl reached the maximum.
综合以上结果，说明本发明具有显著的抗氧化效果。供试物A组各项指标均明显优于其余各组，即由壳寡糖、人参、茯苓、地黄、肉苁蓉、丹参这几种原料组成的复方组合物的抗氧化效果明显优于壳寡糖、人参、茯苓、地黄这几种原料与肉苁蓉、丹参、党参、桃仁、麦冬中的0-1种或两两组合制备得到的复方组合物的抗氧化效果，说明本发明抗氧化效果与本发明特定的原料组成有关，本发明原料配比合理，与本发明特定的原料提取方法一起，使得最终制备得到的复方组合物具有显著的抗氧化效果。Based on the above results, it is indicated that the present invention has a significant antioxidant effect. The indexes of the test substance group A were obviously better than those of the other groups, that is, the antioxidant effect of the compound composition composed of chitosan oligosaccharide, ginseng, Poria, Rehmannia glutinosa, Cistanche deserticola, and Salvia miltiorrhiza was obviously better than that of chitosan oligosaccharide. , ginseng, Poria, Rehmannia glutinosa these several kinds of raw materials and 0-1 kinds or two of the combination of Cistanche, Salvia, Codonopsis, peach kernel, Ophiopogon japonicus, the antioxidant effect of the compound composition prepared by the combination of the antioxidative effect of the present invention and the present invention The specific raw material composition of the present invention is related, the raw material ratio of the present invention is reasonable, and together with the specific raw material extraction method of the present invention, the compound composition finally prepared has a significant antioxidant effect.
(二)人体试服试验(2) Human Trial Test
使用实施例1制备的本发明复合组合物胶囊，对本发明安全性、延缓衰老效果进行检验：Using the composite composition capsules of the present invention prepared in Example 1, the safety and anti-aging effects of the present invention were tested:
受试纳入标准：50-75岁，正常衰老或疾病导致的衰弱、体力和精力不济人员；Inclusion criteria: 50-75 years old, persons with frailty, physical strength and energy due to normal aging or disease;
排除标准：患有以下疾病的人员；慢性过敏性肠炎或功能性腹泻；自身免疫性疾病或免疫缺陷；确诊为HIV、乙肝或丙肝阳性；诊断为严重心肺肾 和肝功能异常史；在过去6个月内发生过重大心血管疾病；医学诊断的神经心理疾病或认知障碍；酗酒，高酒精摄入量的人员。Exclusion criteria: Persons with the following diseases; chronic allergic enteritis or functional diarrhea; autoimmune disease or immunodeficiency; diagnosed HIV, hepatitis B or C positive; diagnosed with a history of severe heart, lung, kidney and liver dysfunction; Major cardiovascular disease within a month; medically diagnosed neuropsychological disease or cognitive impairment; alcoholism, high alcohol intake.
试验设计与分组：采用自身前后对照形式。Experimental design and grouping: self-control before and after.
服用剂量及方法：每日2次，每次3粒，服用量为3.6g/日，连续90天Dosage and method: 2 times a day, 3 capsules each time, the dosage is 3.6g/day, for 90 consecutive days
观察指标：Observation Metrics:
(1)安全性观察：(1) Safety observation:
①血常规：红细胞计数，平均红细胞体积，红细胞分布宽度，平均血红蛋白含量，平均红细胞血红蛋白浓度，白细胞计数，单核细胞计数，单核细胞比例，中性粒细胞计数，淋巴细胞比值，平均血小板体积，血小板压积；①Blood routine: red blood cell count, mean red blood cell volume, red blood cell distribution width, mean hemoglobin content, mean red blood cell hemoglobin concentration, white blood cell count, monocyte count, monocyte ratio, neutrophil count, lymphocyte ratio, mean platelet volume , platelet count;
②尿常规：尿液颜色，尿透明度，尿酸碱度，红细胞，白细胞，尿蛋白，尿酮体，尿糖；②Urine routine: urine color, urine transparency, uric acid alkalinity, red blood cells, white blood cells, urine protein, urine ketones, urine sugar;
③血生化：肝功能的检查：总胆红素、总蛋白质、白蛋白质、球蛋白质、白蛋白/球蛋白比质比例、谷草转氨酶、谷丙转氨酶等；③Blood biochemistry: liver function test: total bilirubin, total protein, albumin, globulin, albumin/globulin ratio, aspartate aminotransferase, alanine aminotransferase, etc.;
④肾功能的检查：肌酸酐(CR)、血中尿素氮(BUN)；④Examination of renal function: creatinine (CR), blood urea nitrogen (BUN);
⑤心电图。⑤ ECG.
(2)功效性观察：(2) Efficacy observation:
①血压皮肤检测：皮肤弹性、胶原蛋白、黑色素异常①Blood pressure skin test: abnormal skin elasticity, collagen and melanin
②血管调节因子：一氧化氮(NO)、血管内皮生长因子(VEGF)② Vascular regulatory factors: nitric oxide (NO), vascular endothelial growth factor (VEGF)
③血清超氧化物歧化酶(SOD)活性、端粒酶(TE)含量③ Serum superoxide dismutase (SOD) activity and telomerase (TE) content
④体验人员跟踪服务量表：④Experience personnel tracking service scale:
衰老症状：共包含4项精力体力不济症状(行走或者活动后疲劳、日常生活中精力体力不济、头晕目眩、睡眠不佳)，根据严重程度分为Ⅰ-Ⅳ级，统计积分值。Aging symptoms: There are 4 symptoms of poor energy and physical strength (fatigue after walking or activities, poor energy and physical strength in daily life, dizziness, poor sleep), which are divided into grades I-IV according to the severity, and the integral value is calculated.
Ⅰ级(0分)：保持一定运动，精力充沛；日常精力充沛；极少头晕目眩，仅在劳累过度后发生；30min内入睡，睡眠时间超过5h，不易惊醒，白天不犯困。Grade I (0 points): maintain a certain amount of exercise, and be energetic; daily energy; rarely dizziness, which occurs only after overwork; fall asleep within 30 minutes, sleep for more than 5 hours, not easy to wake up, and not sleepy during the day.
Ⅱ级(1分)：多行走活动后(如行走2km)稍有疲感；轻微有感觉疲累，日常活动不受影响；一个月仅一两次会发生头晕目眩情况，生活基本不受影响；30min内入睡，睡眠时间少于5h，白天不犯困。Grade II (1 point): Slight feeling of fatigue after more walking activities (such as walking 2km); slight feeling of fatigue, daily activities are not affected; dizziness occurs only once or twice a month, and life is basically not affected; Fall asleep within 30 minutes, sleep less than 5 hours, and not feel sleepy during the day.
Ⅲ级(2分)：介于Ⅱ和Ⅳ之间的感觉；易疲劳，日常活动受到一定影响；每周一两次发生头晕目眩情况，劳累后加重，影响日常生活；超过30min入睡，睡眠时间少于5h，易被惊醒，白天固定时间犯困。Grade III (2 points): feeling between II and IV; easily fatigued, and daily activities are affected to a certain extent; dizziness occurs once or twice a week, aggravated after exertion, affecting daily life; falling asleep more than 30 minutes, less sleep time In 5 hours, it is easy to be awakened and sleepy at a fixed time during the day.
Ⅳ级(3分)：腰背酸软无力，头昏眼花，四肢乏力；疲劳感严重，日常活动严重受限；每天都有晕眩情况，稍有活动后即加重，严重影响日常生活；超过30min入睡，睡眠时间少于5h，半夜经常无故惊醒，白天经常犯困。Grade IV (3 points): weak back, dizziness, weakness of limbs; severe fatigue, severe limitation of daily activities; dizziness every day, aggravated after a little activity, seriously affecting daily life; more than 30 minutes Fall asleep, sleep time is less than 5 hours, often wake up in the middle of the night for no reason, and often feel sleepy during the day.
老年人疾病及亚健康症状：共包含6项(贫血、食欲不振、感冒感染等、精神不安/心悸、畏寒、疼痛)，根据严重程度分为Ⅰ-Ⅳ级，统计积分值。Diseases and sub-health symptoms of the elderly: a total of 6 items (anemia, loss of appetite, cold infection, etc., mental restlessness/palpitations, chills, pain) are divided into grades I-IV according to the severity, and the integral value is calculated.
Ⅰ级(0分)：无症状。Grade I (0 points): asymptomatic.
Ⅱ级(1分)：进食欲望低，但还可以正常进食；轻微畏寒；轻微贫血，营养补充后不影响生活；有轻微痛感；每月仅一两次精神不安/心悸，能胜任一般日常活动，在稍重体力活动时，心悸加重；偶尔感冒，仅换季或劳累后容易生病。Grade II (1 point): low desire to eat, but can eat normally; mild chills; mild anemia, which does not affect life after nutritional supplementation; mild pain; mental restlessness/palpitations only once or twice a month, capable of normal daily life During physical activity, palpitations are aggravated; occasionally catch a cold, and it is easy to get sick only after changing seasons or exertion.
Ⅲ级(2分)：进食困难，有营养不良风险；较严重畏寒，与正常人存在明显差异；中度贫血；具体部位有较重的疼痛感；每周一两次精神不安/心悸，活动量稍大(行走2km)心悸严重，伴有精神不安；感冒频率介于Ⅱ和Ⅳ之间。Grade III (2 points): Difficulty eating, at risk of malnutrition; severe chills, significantly different from normal people; moderate anemia; severe pain in specific parts; mental restlessness/palpitations, activity once or twice a week Slightly larger (walking 2km), severe palpitations, accompanied by mental restlessness; the frequency of colds is between II and IV.
Ⅳ级(3分)：完全不思进食，严重营养不良；极度畏寒，严重影响生活；严重贫血，需要药物维持正常生活；全身疼痛，严重影响生活质量；每天心悸，精神紧张，轻微活动即感心悸；经常性感冒，生病频繁，抵抗力差。Grade IV (3 points): No appetite at all, severe malnutrition; extreme chills, seriously affecting life; severe anemia, requiring drugs to maintain normal life; body pain, seriously affecting the quality of life; daily heart palpitations, mental stress, mild activity Feeling palpitations; frequent colds, frequent illnesses, and poor immunity.
表2试食前一般状况Table 2 General condition before trial
Figure PCTCN2020120583-appb-000003
Figure PCTCN2020120583-appb-000003
表3试食前后血常规检查结果分析(X±SD)Table 3 Analysis of the results of routine blood tests before and after the food trial (X±SD)
Figure PCTCN2020120583-appb-000004
Figure PCTCN2020120583-appb-000004
表4试食前后肝肾功能及血液生化指标结果分析(X±SD)Table 4 Analysis of the results of liver and kidney function and blood biochemical indexes before and after the trial (X±SD)
Figure PCTCN2020120583-appb-000005
Figure PCTCN2020120583-appb-000005
Figure PCTCN2020120583-appb-000006
Figure PCTCN2020120583-appb-000006
表5试食前后心率检查结果分析(X±SD)Table 5 Analysis of heart rate inspection results before and after the food trial (X±SD)
Figure PCTCN2020120583-appb-000007
Figure PCTCN2020120583-appb-000007
受试者试食前、试食30天后胸透、心电图、腹部B超及尿常规检查均未见明显异常。试食期间，受试者未见不良反应或过敏反应等症状。No obvious abnormality was found in the chest X-ray, electrocardiogram, abdominal B-ultrasound and routine urine examination before and 30 days after the test. During the trial period, the subjects had no symptoms such as adverse reactions or allergic reactions.
试验一：Test one:
表6：复方组合物对改善衰老症状、老年人疾病及亚健康症状的有效率Table 6: Effective rate of compound composition on improving symptoms of aging, diseases of the elderly and sub-health symptoms
Figure PCTCN2020120583-appb-000008
Figure PCTCN2020120583-appb-000008
从上表6可以看出，复方组合物对衰老症状、老年人疾病及亚健康症状具有改善作用，且随着服用时间的延长，其有效率也是逐渐增大的；服用复方组合物60天后，对改善衰老症状的总有效率可达100％，说明本发明的复方组合物对衰老的改善效果极显著。As can be seen from the above table 6, the compound composition has an improving effect on the symptoms of aging, senile diseases and sub-health symptoms, and along with the prolongation of the taking time, its effective rate is also gradually increased; after taking the compound composition for 60 days, The total effective rate for improving aging symptoms can reach 100%, indicating that the compound composition of the present invention has a very significant improving effect on aging.
试验二：Test two:
表7：复方组合物对改善老年人皮肤状况的有效率Table 7: Effectiveness of compound composition for improving skin condition of the elderly
Figure PCTCN2020120583-appb-000009
Figure PCTCN2020120583-appb-000009
上述表7对受试者的皮肤状况进行检测发现，此复方组合物对老年人皮肤弹性、胶原蛋白、黑色素异常状况均有一定改善作用，并且其改善有效率随着服用时间的延长而增强。The above-mentioned table 7 detects the skin condition of the subject and finds that the compound composition has a certain improvement effect on the skin elasticity, collagen and melanin abnormal conditions of the elderly, and the improvement effective rate increases with the prolongation of taking time.
试验三：Test three:
表8：复方组合物对改善老年人体内抗衰老酶含量的影响Table 8: The effect of compound composition on improving the content of anti-aging enzymes in the elderly
Figure PCTCN2020120583-appb-000010
Figure PCTCN2020120583-appb-000010
注：与0天相比*p﹤0.05；与0天相比**p﹤0.01Note: compared with 0 days *p﹤0.05; compared with 0 days **p﹤0.01
上述表8对受试者体内的抗衰老酶含量进行检测发现，服用复方组合物时间越久，其体内的超氧化物歧化酶和端粒酶的含量越高，说明本发明的复方组合物可以有效提高老年人体内的抗衰老酶含量。The above-mentioned table 8 detects the anti-aging enzyme content in the subject's body and finds that the longer the compound composition is taken, the higher the content of superoxide dismutase and telomerase in its body, indicating that the compound composition of the present invention can be effective. Increase the content of anti-aging enzymes in the elderly.
表9：复方组合物对改善老年人体内抗衰老酶的有效率Table 9: Effectiveness of compound composition on improving anti-aging enzymes in the elderly
Figure PCTCN2020120583-appb-000011
Figure PCTCN2020120583-appb-000011
通过上表9中数据可知，本发明公开保护的复方组合物对改善老年人体内抗衰老酶有效率在受试第90天达最高，超氧化物歧化酶及端粒酶提高有效率分别为90.08％，86.07％，说明本发明的复方组合物会随着服用时间的延长逐步改善老年人体内的抗衰老酶的有效率，具有较好的抗氧化作用。As can be seen from the data in Table 9 above, the effective rate of the compound composition disclosed and protected in the present invention for improving anti-aging enzymes in the elderly reached the highest on the 90th day of the test, and the effective rates of superoxide dismutase and telomerase were respectively 90.08 %, 86.07%, indicating that the compound composition of the present invention can gradually improve the effective rate of anti-aging enzymes in the elderly with the prolongation of taking time, and has a good anti-oxidation effect.
试验四：Test four:
表10：复方组合物对改善老年人体内血管调节因子含量的影响Table 10: The effect of compound composition on improving the content of vascular regulatory factors in the elderly
Figure PCTCN2020120583-appb-000012
Figure PCTCN2020120583-appb-000012
注：与0天相比**p﹤0.01Note: Compared with 0 days **p﹤0.01
由上述表10测定受试者的体内调节因子含量可知，服用本方法公开制备的复方组合物人群体内的一氧化氮和内皮生长因子含量均呈现上升趋势，且随着服用时间的延长而增多，说明此复方组合物具有增加体内血管调节因子含量的功效。It can be known from the above-mentioned Table 10 that the content of the regulatory factor in the test subject is measured, and the content of nitric oxide and endothelial growth factor in the people who take the compound composition disclosed and prepared by this method all presents an upward trend, and increases with the prolongation of the taking time, It is indicated that the compound composition has the effect of increasing the content of vascular regulatory factors in the body.
表11：复方组合物对改善老年人体内血管调节因子的有效率Table 11: Effectiveness of the compound composition on improving vascular regulatory factors in the elderly
Figure PCTCN2020120583-appb-000013
Figure PCTCN2020120583-appb-000013
由上表11数据可知，复方组合物对改善老年人体内血管调节因子的有效率是随着时间的延长而增加的，在受试的第90天，总有效率可达99.2％，一氧化氮和内皮生长因子提高有效率分别为97.10％，96.04％，提示本发明的复方组合物具有扩张血管，促进血管再生，保护心脑血管的作用。From the data in Table 11 above, it can be seen that the effective rate of the compound composition for improving vascular regulatory factors in the elderly increases with time. On the 90th day of the test, the total effective rate can reach 99.2%, nitric oxide and endothelial growth factor, the effective rates were 97.10% and 96.04%, respectively, suggesting that the compound composition of the present invention has the functions of dilating blood vessels, promoting blood vessel regeneration, and protecting cardiovascular and cerebrovascular.
综合上述实验结果分析可知，本发明公开保护的复方组合物具有显著的延缓衰老效果，可以有效改善老年人的衰老体征，包括衰老、疾病及亚健康症状，有效率极高，总体有效率可达100％；可以有效改善老年人的皮肤状况，同时对老年人体内抗衰老酶含量、血管调节因子含量均有增强效果。Based on the analysis of the above experimental results, it can be seen that the compound composition disclosed and protected in the present invention has a significant anti-aging effect, can effectively improve the aging signs of the elderly, including aging, disease and sub-health symptoms, and has a very high effective rate, and the overall effective rate can reach 100%; it can effectively improve the skin condition of the elderly, and at the same time, it can enhance the content of anti-aging enzymes and vascular regulatory factors in the elderly.
以上结果表征，本发明公开保护的复方组合物具有抗氧化、延缓衰老的功效，该复方组合物无毒副作用、易吸收，可用于延缓衰老，修复DNA损伤、抗氧化损伤，还能降低老年病的发生风险，适于市面推广与应用。The above results indicate that the compound composition disclosed and protected in the present invention has the effects of anti-oxidation and anti-aging. The compound composition has no toxic and side effects, is easy to absorb, and can be used to delay aging, repair DNA damage, resist oxidative damage, and reduce senile diseases. The risk of occurrence is suitable for market promotion and application.
对所公开的实施例的上述说明，使本领域专业技术人员能够实现或使用本发明。对这些实施例的多种修改对本领域的专业技术人员来说将是显而易见的，本文中所定义的一般原理可以在不脱离本发明的精神或范围的情况下，在其它实施例中实现。因此，本发明将不会被限制于本文所示的这些实施例，而是要符合与本文所公开的原理和新颖特点相一致的最宽的范围。The above description of the disclosed embodiments enables any person skilled in the art to make or use the present invention. Various modifications to these embodiments will be readily apparent to those skilled in the art, and the generic principles defined herein may be implemented in other embodiments without departing from the spirit or scope of the invention. Thus, the present invention is not intended to be limited to the embodiments shown herein, but is to be accorded the widest scope consistent with the principles and novel features disclosed herein.

Claims (9)

  1. 一种具有抗氧化、延缓衰老功效的复方组合物，其特征在于，所述复方组合物是由中药提取物与壳寡糖按照质量比(3～8)：1混合而成；A compound composition with anti-oxidation and anti-aging effects, characterized in that the compound composition is formed by mixing Chinese herbal extracts and chitosan oligosaccharides in a mass ratio of (3-8):1;
    其中，所述中药提取物是由以下中药材单独提取后混合而得，按照质量百分比计：Wherein, the traditional Chinese medicine extract is obtained by mixing the following Chinese medicinal materials after separate extraction, in terms of mass percentage:
    人参7～15％；Ginseng 7～15%;
    茯苓14～35％；Poria 14～35%;
    地黄14～35％；Rehmannia 14～35%;
    肉苁蓉14～35％；Cistanche 14～35%;
    丹参7～15％；Salvia 7～15%;
    党参0～10％；Codonopsis 0 to 10%;
    桃仁0～10％；Peach kernel 0～10%;
    麦冬0～10％。Ophiopogon japonicus 0 to 10%.
  2. 根据权利要求1所述的一种具有抗氧化、延缓衰老功效的复方组合物，其特征在于，所述中药提取物是由以下中药材单独提取后混合而得，按照质量百分比计：A compound composition with anti-oxidation and anti-aging effects according to claim 1, characterized in that, the Chinese herbal extract is obtained by mixing the following Chinese herbal medicines after being extracted individually, in mass percent:
    人参12～15％；Ginseng 12～15%;
    茯苓25～30％；Poria 25～30%;
    地黄20～25％％；Rehmannia 20～25%%;
    肉苁蓉20～25％；Cistanche 20～25%;
    丹参12～15％；Salvia 12～15%;
    党参2～3％；Codonopsis 2 to 3%;
    桃仁1～2％；1～2% of peach kernel;
    麦冬1～2％。Ophiopogon japonicus 1 to 2%.
  3. 根据权利要求1或2所述的一种具有抗氧化、延缓衰老功效的复方组合物，其特征在于，所述中药提取物是由以下中药材单独提取后混合而得，按照质量百分比计：A kind of compound composition with anti-oxidation and anti-aging effect according to claim 1 or 2, it is characterized in that, described Chinese herbal medicine extract is obtained by following Chinese herbal medicines extracted separately and then mixed, according to mass percentage:
    人参13％；Ginseng 13%;
    茯苓26％；Poria 26%;
    地黄22％％；Rehmannia 22%%;
    肉苁蓉22％；Cistanche 22%;
    丹参13％；Salvia 13%;
    党参2％；Codonopsis 2%;
    桃仁1％；Peach kernel 1%;
    麦冬1％。Ophiopogon japonicus 1%.
  4. 一种如权利要求1～3任一所述的具有抗氧化、延缓衰老功效的复方组合物的制备方法，其特征在于，包括：将人参、茯苓、地黄、肉苁蓉、丹参、党参、桃仁和麦冬分别提取、纯化、浓缩及喷雾干燥制得中药提取物后与壳寡糖混合均匀制得；具体包括如下步骤：A method for preparing a compound composition with anti-oxidative and anti-aging effects as claimed in any one of claims 1 to 3, characterized in that, comprising: combining ginseng, Poria, Rehmannia glutinosa, Cistanche deserticola, Salvia miltiorrhiza, Codonopsis pilosula, peach kernel and wheatgrass Extracting, purifying, concentrating and spray-drying to obtain the traditional Chinese medicine extract, and then mixing it with chitosan oligosaccharide to obtain it; specifically, it includes the following steps:
    (1)将中药材粉碎过筛后与乙醇溶液按照配比加热回流提取、过滤，并将药渣多次提取后的提取液合并，备用；(1) After the Chinese medicinal materials are pulverized and sieved, they are heated and refluxed for extraction and filtration with ethanol solution according to the proportion, and the extracts after multiple extractions of the medicinal residues are combined for subsequent use;
    (2)将步骤(1)合并的所述提取液纯化、浓缩后喷雾干燥或真空干燥，过筛得到中药提取物；(2) spray-drying or vacuum-drying after purifying and concentrating the described extract that step (1) is merged, obtain Chinese medicine extract by sieving;
    (3)将步骤(2)中所述中药提取物按照如权利要求1公开的质量配比与所述壳寡糖混合均匀，得到具有抗氧化、延缓衰老功效的复方组合物。(3) The traditional Chinese medicine extract in the step (2) is uniformly mixed with the chitosan oligosaccharide according to the mass ratio disclosed in claim 1 to obtain a compound composition with anti-oxidation and anti-aging effects.
  5. 根据权利要求4所述的一种具有抗氧化、延缓衰老功效的复方组合物的制备方法，其特征在于，所述步骤(1)中，中药材粉碎过筛目数为20～80目，添加中药材与乙醇溶液的体积比为1：(5～20)，且中药材加热回流提取次数为1～3次，提取时间为1～3h，提取温度为80℃～100℃。The preparation method of a compound composition with anti-oxidation and anti-aging effects according to claim 4, wherein in the step (1), the Chinese medicinal materials are crushed and sieved with a mesh number of 20 to 80 meshes, and added The volume ratio of the Chinese medicinal material to the ethanol solution is 1: (5-20), and the extraction times of the Chinese medicinal material by heating and refluxing are 1-3 times, the extraction time is 1-3 hours, and the extraction temperature is 80-100°C.
  6. 根据权利要求4所述的一种具有抗氧化、延缓衰老功效的复方组合物的制备方法，其特征在于，所述步骤(2)中，喷雾干燥温度为180℃～200℃，真空干燥温度为50℃～100℃，过筛目数为60～80目。The method for preparing a compound composition with anti-oxidation and anti-aging effects according to claim 4, wherein in the step (2), the spray drying temperature is 180°C to 200°C, and the vacuum drying temperature is 50℃～100℃, the sieving mesh number is 60～80 meshes.
  7. 根据权利要求4或6所述的一种具有抗氧化、延缓衰老功效的复方组合物的制备方法，其特征在于，所述步骤(2)还包括喷雾干燥或真空干燥前向浓缩后的提取液中添加β-环糊精混合均匀步骤；其中所述β-环糊精添加量为所述中药材质量的1～20％。The method for preparing a compound composition with anti-oxidation and anti-aging effects according to claim 4 or 6, wherein the step (2) further comprises the concentrated extract before spray drying or vacuum drying The step of adding β-cyclodextrin to mix evenly in the middle; wherein the added amount of the β-cyclodextrin is 1-20% of the quality of the Chinese medicinal material.
  8. 一种如权利要求1～3任一所述的具有抗氧化、延缓衰老功效的复方组合物或如权利要求4～7任一所述方法制备的复方组合物在制备保健食品中的应用。A compound composition with anti-oxidation and anti-aging effects as claimed in any one of claims 1 to 3 or the application of the compound composition prepared by the method as claimed in any one of claims 4 to 7 in preparing health food.
  9. 根据权利要求8所述的一种具有抗氧化、延缓衰老功效的复方组合物的应用，其特征在于，所述复方组合物可以作为膳食补充剂或保健食品的原料，且所述复方组合物的剂型为胶囊剂、颗粒剂或片剂。The application of a compound composition with anti-oxidation and anti-aging effects according to claim 8, wherein the compound composition can be used as a raw material for dietary supplements or health food, and the compound composition has The dosage form is capsule, granule or tablet.
PCT/CN2020/120583 2020-09-24 2020-10-13 Compound composition with anti-oxidation and anti-aging effects, preparation method therefor and application thereof WO2022061978A1 (en)

Priority Applications (1)

Application Number Priority Date Filing Date Title
US17/207,740 US20220087926A1 (en) 2020-09-24 2021-03-22 Compound composition with anti-oxidation and anti-aging effects and preparation method and application thereof

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
CN202011016232.8 2020-09-24
CN202011016232.8A CN112137088A (en) 2020-09-24 2020-09-24 Compound composition with antioxidant and anti-aging effects and preparation method and application thereof

Related Child Applications (1)

Application Number Title Priority Date Filing Date
US17/207,740 Continuation US20220087926A1 (en) 2020-09-24 2021-03-22 Compound composition with anti-oxidation and anti-aging effects and preparation method and application thereof

Publications (1)

Publication Number Publication Date
WO2022061978A1 true WO2022061978A1 (en) 2022-03-31

Family

ID=73896577

Family Applications (1)

Application Number Title Priority Date Filing Date
PCT/CN2020/120583 WO2022061978A1 (en) 2020-09-24 2020-10-13 Compound composition with anti-oxidation and anti-aging effects, preparation method therefor and application thereof

Country Status (2)

Country Link
CN (1) CN112137088A (en)
WO (1) WO2022061978A1 (en)

Families Citing this family (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN110477367A (en) * 2019-09-24 2019-11-22 新疆华春生物药业股份有限公司 A kind of health composition and preparation method thereof

Citations (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN108684884A (en) * 2018-05-23 2018-10-23 南京中生生物科技有限公司 A kind of composition and preparation method thereof of chitosan oligosaccharide, green-tea extract

Family Cites Families (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN103830558B (en) * 2012-11-26 2017-04-26 富力 Anti-aging composition and preparation method thereof
CN104223297B (en) * 2014-09-05 2016-09-14 杨高林 A kind of schisandra chinensis health-care oral liquid of slow down aging and preparation method thereof
CN105412353A (en) * 2015-09-11 2016-03-23 皮山御盛金茂生物科技有限公司 Traditional Chinese medicine combination with functions of resisting senility, improving immunity, resisting fatigue and keeping healthy
CN106266898A (en) * 2016-09-27 2017-01-04 杭州本草养正堂生物科技有限公司 A kind of vital energy benefiting and the kidney invigorating, the compound preparation and preparation method thereof of defying age

Patent Citations (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN108684884A (en) * 2018-05-23 2018-10-23 南京中生生物科技有限公司 A kind of composition and preparation method thereof of chitosan oligosaccharide, green-tea extract

Non-Patent Citations (4)

* Cited by examiner, † Cited by third party
Title
CHEN YAOHUA: "Passage; The golden key of human health - chitosan oligosaccharide", HEALTH TIMES, 25 September 2008 (2008-09-25), CN, pages 013, XP009535597 *
LIU HUANLAN , QU WEILING , WEN ZHE: "Interpretation of Qiongyu Gao's Anti-aging Prescriptions", CHINA PRACTICAL MEDICINE, vol. 5, no. 17, 20 June 2010 (2010-06-20), pages 210 - 211, XP055915590, DOI: 10.14163/j.cnki.11-5547/r.2010.17.026 *
ZHOU WENQUAN , LIU JIANHUA , ZHOU HONG: "A Review of Anti-aging Drugs in Modern Chinese Medicine", ACTA CHINESE MEDICINE AND PHARMACOLOGY, vol. 6, no. 4, 29 August 1991 (1991-08-29), pages 43 - 49, XP055915593 *
ZUO ZHIQIN , SHEN ZHIHUA: "Eight Methods and Prescriptions for Anti-Aging in Transitional Chinese Medicine", JIANGXI JOURNAL OF TRADITIONAL CHINESE MEDICINE, vol. 40, 15 May 2009 (2009-05-15), pages 11 - 13, XP055915587 *

Also Published As

Publication number Publication date
CN112137088A (en) 2020-12-29

Similar Documents

Publication Publication Date Title
CN101940740B (en) Chinese medicinal preparation for treating anemia
CN102205107B (en) Chinese medicinal preparation for treating duodenal ulcer and preparation method thereof
US20220087926A1 (en) Compound composition with anti-oxidation and anti-aging effects and preparation method and application thereof
US9707262B2 (en) Composition with anoxia-tolerant and anti-fatigue effects and use thereof
CN106509887A (en) Fatigue preventing health-care composition and a preparation method thereof
CN105029419A (en) Healthcare function food
CN106798214A (en) A kind of hippophae rhamnoides beverage and preparation method thereof
WO2022061978A1 (en) Compound composition with anti-oxidation and anti-aging effects, preparation method therefor and application thereof
CN104431772A (en) Flour-made food capable of lubricating intestines and detoxifying and preparation method of flour-made food
CN107156820A (en) Conditioning women postpartum is damaged nutraceutical of constitution and preparation method thereof comprehensively
CN101129699A (en) Guiyin pill of long-cultivated land
CN111467468A (en) Concentrated nutrient solution containing ginseng, cordyceps militaris, ginger and wolfberry fruit and preparation method thereof
CN105920269A (en) Health-care medicinal liquor for females
CN106928376A (en) The separation method of skunk bush polysaccharide and its application
CN102784230A (en) Pharmaceutical composition preparation for treating nutritional anemia
CN105533749A (en) Health food containing herba epimedii and fructus schizandrae and preparing method and application thereof
CN104887759A (en) Ginseng powder wine and preparation method thereof
CN111407850A (en) Plant selenium sealwort tablet and preparation method thereof
CN104587300A (en) Traditional Chinese medicine composition for treating acute leukemia and preparation method of traditional Chinese medicine composition
CN110025011A (en) A kind of Radix Ophiopogonis ginseng lozenge of strengthen immunity
CN115607629B (en) Traditional Chinese medicine composition with liver protecting and alcohol effect dispelling functions and preparation method thereof
CN104000180A (en) Ginseng compound assisting in blood sugar level regulation and preparing method and application thereof
CN111346172B (en) Pharmaceutical composition for improving immunity
CN101224004A (en) Medicinal granules for the elderly to lose weight and preparing method thereof
CN106309920A (en) Traditional Chinese medicine preparation for relieving fatigue and preparation method thereof

Legal Events

Date Code Title Description
121 Ep: the epo has been informed by wipo that ep was designated in this application

Ref document number: 20954824

Country of ref document: EP

Kind code of ref document: A1

NENP Non-entry into the national phase

Ref country code: DE

122 Ep: pct application non-entry in european phase

Ref document number: 20954824

Country of ref document: EP

Kind code of ref document: A1